One-way mixed lymphocyte culture (MLC) tests were performed among the members of five chimpanzee harems in all possible combinations: parents, parent-child, siblings and half-siblings. The technical aspects of MLC testing in chimpanzees appeared to be very similar to those observed for human and rhesus monkey MLC's. Two unexpected observations were made for which no satisfactory explanation can as yet be given: firstly, the occurrence of animals with consistently high autologous values and secondly, the existence of chimpanzees displaying low MLC responsiveness. The high autologous values occurred mostly in older imported animals (25% with high autologous values), while only one of the 45 laboratory born animals showed this phenomenon. Low responsiveness occurred in a few offspring belonging to a single harem only and is therefore likely to be genetically controlled but, as it appeared, not by genes linked to ChLA. Data suggesting the existence of an MHC-linked "major MLC" or D locus were confirmed and extended. A gene dose effect for D iocus antigens was demonstrable, i.e., combinations of related animals differing for one showed lower MLC responses than combinations differing for two ChLA haplotypes. The number of D locus alleles was estimated to be 10.