The binding of progesterone to plasma and endometrial cytosol is markedly influenced by Zn++, the degree and magnitude of this influence being dependent on the concentration of the metal ion. There is a critical protein concentration (approximately 10 mg/ml) beyond which the zinc exerts either a stimulatory or inhibitory effect. Maximum increases in binding of over 60% were attained in solutions of plasma containing 30 mg of protein whereas increases of 10% were measured in cytosol specimens with 10 mg protein/ml. This metal mediated effect was however progressively diminished with increasing zinc concentration resulting finally in the return of the binding to the levels observed in the absence of added Zn++. The zinc induced inhibition was most evident in plasma and cytosol with a protein concentration less than 10 mg/ml. The magnitude of this effect was inversely proportional to the levels of protein in solution. Scatchard analysis of the data revealed that the number of progesterone binding sites in the receptor are affected by the presence of the metal while the association constants remained unchanged. The study also suggests that the zinc induced changes are partially reversed by dithiothreitol and EDTA. We believe that the metal interferes directly with the SH groups at the receptor binding sites.