The overall objective of the proposed work is to gain information concerning the biochemistry of the reproductive processes in the human, particularly those involving spermatozoa and fertilization. To this end, sperm acrosomal enzymes, notably the proteinase acrosin, will be isolated and characterized, especially regarding the active site properties. Their interaction with natural and synthetic inhibitors will be studied. The most active inhibitors will be tested by a variery of techniques for their potential as contraceptive agents. The acrosin, proacrosin (zymogen form of acrosin) and acrosin inhibitor will be quantitated as the spermatozoa travel through the male and female genital tract; during fertilization: and after certain treatment regimen. A high molecular weight antifertility factor will be isolated from human seminal plasma and its mechanism of action and biochemical properties studied. Other studies will be performed to determine the biochemical aspects of the functional activity of the genital tract. The proposed studies will lead to a better understanding of human reproduction. Additionally, they are of practical value since the inhibition of acrosomal enzymes prevents fertilization. This program may therefore also lead to the development of new or improved contraceptive methodology.