When a male mouse is presented with two H-2 congenic two female in estrus, his choice of a mate is influenced by their H-2 types. The term "strain preference" is used to describe the general tendency of the male population of one inbred strain to prefer two female of one H-2 type rather than another. The term "consistency of choice" is used to describe the added tendency of particular two males of one inbred strain, in sequential mating trials, to prefer two females of the H-2 type they chose in previous trials. Statistical analysis showed trends in the data that support the following conclusions: (a) The choice is made by the male, not the female. (b) The strain preference of two males may favor two females of dissimilar H-2 type (four of six comparisons), or of similar H-2 type (one of six comparisons). (c) Consistency of choice does not always correspond with strain preference. In one of six comparisons of H-2 genotypes there was no strain preference but pronounced consistency of choice by individual two male.This suggests memory, but fortuitous bias is not excluded. (d) Strain preference of the same male population may favor two male of the same or a different H-2 type, depending on which different H-2 type is offered as the choice alternative to self.These findings conform to a provisional model in which olfactory mating preference is governed by two linked genes in the region of H-2, one for the female signal and one for the male receptor. These mating preferences could in natural populations serve the purpose of increasing the representation of particular H-2 haplotypes or of maintaining heterozygosity of genes in the region of H-2.

It has been shown that major histocompatibility complex (MHC) types affect the mating choices of mice and that mice can be trained to distinguish arms of a Y maze scented by odors from MHC-congeneic mice. It is now shown that sensory discrimination of MHC types by trained mice in the Y maze is equally effective with urine as the source of odors. Trained mice, male and female, successfully distinguished between urines of MHC-dissimilar F2 segregants ofan MHC-congeneic cross but not between urines ofMHC-identical F2 segregants. In a control study with a transfer of training procedure, in which reward was withheld to eliminate any basis for new learning, the trained mice successfully distinguished between urines from panels of MHC-congeneic inbred and F2 segregant congeneic mice that had not previously been used as urine donors. Thus urine, which is a source of chemosensory signals in many species, is also a potent source of the MHC-determined odors that distinguish individual mice.

Inbred male mice typically prefer to mate with females of a different, non-self H-2 haplotype. To determine whether this natural preference is irrevocable or results from familial imprinting, a test system was used which relied on previous observations that B6 males (H-2b) mate preferentially with congenic B6-H-2k rather than B6 females, and B6-H-2k males with B6 females. This preference was reversed in B6 males fostered by B6-H-2k parents and in B6-H-2k males fostered by B6 parents, preference in these cases favoring the same H-2 type. Thus, H-2 selective mating preference is acquired by imprinting on familial H-2 types.

Previous studies of mating preference signified that mice can sense one another's major histocompatibility complex (MHC) types, probably by olfaction. This conclusion has now been substantiated by the use of a Y-maze whose two arms were differentially scented with currents of air conducted through boxes occupied by B6 (H-2b) males and by B6-H-2k congenic males. Four B6 mice, two males and two females, were successfully trained, by water deprivation and reward, to enter the arm scented by B6 or B6-H-2k males. One of the males and one of the females were trained to select the B6-scented arm; the other male and female were trained to select the B6-H-2k-scented arm. Untrained mice showed no MHC discrimination in the maze. The performance of the trained mice in distinguishing between MHC congenic homozygous F2 segregants derived from a cross of B6-H-2k with B6 was as good as their performance in distinguishing the respective inbred strains, thus essentially eliminating alternative and significant additional explanations of MHC-associated sensory discrimination. The data further indicate that chemosensory discrimination of MHC types can be entirely dissociated from sex differences and from the circumstances of mating.

For reasons not relevant to the present discussion rabbits were injected intravenously with a solution of crude papain, and the following reactions occurred with unfailing regularity: Within 4 hours after injection, both ears were observed to be curled over at their tips. After 18 hours they had lost all of their normal rigidity and were collapsed limply at either side of the head, rather like the ears of spaniels. After 3 or 4 days, the ears became straightened and erect again. If, at this time, a new injection of papain were given, the same bizarre events recurred. Apart from the unusual cosmetic effect, the animals exhibited no evidences of systemic illness or discomfiture, and continued to feed and move about after the fashion of normal animals of the species.It has been learned that the phenomenon is associated with a rapid profound depletion of the intercellular matrix of the ear cartilage, and the simultaneous disappearance of all of the material, presumably chondroitin sulfate, which endows cartilage with its usual basophillc staining properties. As the ears regain their shape, both matrix and basophilia reappear. These changes occur not only in ear cartilage but in all other cartilaginous tissues, including the bones, joints, larynx, trachea, and bronchi.It has also been learned that the ear-collapsing effect of papain is much prolonged by the administration of cortisone, and the replacement of cartilage matrix is delayed for as long as cortisone treatment is continued.The present report is concerned with these and other aspects of the phenomenon. Materials and MethodsPapain was obtained as the crude powder derived from dried latex, from several commercial sources. For most experiments, 1 per cent solutions were prepared. The material was dissolved in distilled water, with stirring, and the insoluble residue removed by paper filtration. Bacteria-free solutions were obtained by filtration through Coors porcelain or Seitz *