PIP: Immunocontraception, the inhibition of fertility by immunologic methods, is predicated on the concept that if a protein (antigen) specific to the reproductive system can be identified and isolated, monospecific antibodies directed against this antigen can possibly inhibit its reproductive role and thus inhibit fertility. This chapter discusses an immunocontraceptive approach to fertility regulation based upon a component present in the zona pellucida, a noncellular, gelatinlike layer surrounding the mammalian oocyte and preimplantation embryo. Several studies have unequivocally demonstrated the contraceptive nature of the zona-antizona reaction. Zona pellucida is a potent heteroimmunogen which contains at least one tissue-specific but not species-specific antigen; thus, antibodies directed against this antigen are monospecific, not cross reacting with other tissues. Species whose zonae are immunologically similar to human zonae have been identified (e.g., pig, cow, rabbit), and techniques are available for collecting large quantities of zona material from these species. Also, a sensitive and sophisticated radioimmunoassay system for detecting zona antigens has been developed. Thus, the potential exists for critical evaluation of the zona-antizona immunocontraceptive approach and fertility regulation. Future research should focus on the effect of heteroimmunization with zona on fertility, utilizing zona that are both antigenically similar to the human zona and which are available in sufficient quantities for consideration as sources of zona antigen for possible future application in human contraceptive studies. There is also a need to purify individual zona antigens biochemically, followed by evaluation of such purified antigens as effective immunogens for inhibiting fertility and also the resulting antisera for monospecificity toward zona.