Steroid compounds form dissociable complexes of low binding energy with numerous proteins of different origin as can be demonstrated by various physicoehemical procedures. This interaction has definite physiological consequences in case of the steroid hormones. The sites of attachment between A~-3-ketosteroids and human serum albumin appear to be located at the alpha side of the steroid molecule. The affinity of interaction with serum albumins is increased by entrance of electron-repelling groups (alkyl) into the steroid, and decreased by electron-attracting groups (--OH ; =0 ; halogen) ("polarity rule"). This rule is reversed in interactions with certain proteins which have a higher content of aliphatic hydroxyl groups. It was concluded from competition studies with higher fatty acids that the attachment os A4-3-kctosteroids to serum albumin does not take place at the anion-binding sites. The SH-group of serum albumin is not involved in the interaction with testosterone.The al-acid glyeoprotein (orosomucoid) from human serum was found to have a particularly high binding affinity for progesterone. Removal of sialie acid results in a decrease of this binding affinity. Complex formation with the orosomueoid leads to physiological inactivation of progesterone.A highly specific interaction occurs between the adrenocorticoid hormones and the corticosteroidbinding globulin (transcortin) in serum of human and other species. For a quantitative test, the endogenous corticosteroids have to be removed by dialysis at 37C. Cortisol, corticosterone and related hormones are bound by transcortin; aldo-"/1This work supported by Public Health Service research grants (AM-04040, AM-06369), a research career program award (5-K6-GM-14, 138) and a research contract of the Dept. of the Army, U.S, Army IViedical l~es. and Dev. Oommand (DA-49-193-1YiD-2263).For a review of the work on steroid protein interactions up to beginning of 1960 see (1). 481 sterone interacts with serum and transcortincontaining fractions more strongly than with albumin. The "transeortin" activity of rat serum increases after adrenalectomy and hypophysectomy; injection of cortieosterone into adrenalectomized rats reverses this effect. The general increase of the total a-globulin fraction in adrenaleetomized rats (15-16%) is smaller than the increase ill "transcortin '~ activity (100%). The cortieosteroid-binding serum proteins of different mammalian species (rat, rabbit, steer, horse) were found to be a-globulins. Their binding affinities towards different corticosteroids will be discussed. INDEX 481 LIPI])-PROTEIN IN~ERACTI()N, by D. G. Therriault 485 BINDINQ Or S~OIDS TO PROTEINS, by Ulrich Westphal