The specificity of guinea pig progesterone- binding protein (transprogestin.) has been determined for 100 different steroids and a variety of drugs. Of the steroids known to be present in mammalian blood, only deoxycorticosterone and 20α-dihydroprogesterone competed strongly, 5α-dihydrotestosterone less strongly, and testosterone, 20β-dihydroprogesterone and cortisol weakly. All competing compounds possessed a 3-keto group. Demethylation at C-10 and methyl - ation at C-4, C-6 and C-17 increased binding. 17β-Hydroxysteroids were bound more strongly than 17-keto or 17α-hydroxysteroids. Hydroxylation generally decreased binding as did 5P-reduction, fluoride substitution, sulfation and aromatization. The drugs tested did not show any binding at concentrations equal to or above usual therapeutic serum levels. Only two compounds, both synthetic, demonstrated greater affinity for the binding protein than progesterone, these being medrogestone (6,17α-dimethylpregn-4,6-diene-3,20-dione) and 17β-OH-4,4-dimethylestr-5-ene-3-one. (Endocrinology94: 122, 1974)