The murine zona pellucida surrounds the growing oocyte, ovulated egg and dividing embryo. It is comprised of three sulfated glycoproteins designated ZP-1, ZP-2, and ZP-3 which have molecular weights of 185,000, 140,000 and 83,000 daltons respectively. We have isolated a series of cell lines that produce monoclonal antibodies to ZP-2 and to ZP-3. These immunogical probes indicate that the extracellular matrix proteins of the zona pellucida are found uniquely in the ovary where they surround maturing oocytes. We have demonstrated that passive immunization with antibodies specific either for ZP-2 or ZP-3 inhibit in vivo and in vitro fertilization. This effect is observed with ng/ml quantities of antibody. It appears that the antibodies do not preclude sperm binding but rather prevent sperm penetration of the zona by steric hinderance. Although long-term, the contraceptive effect is fully reversible and this reversibility is associated with loss of antibody from the zona pellucida surrounding intra-ovarian oocytes. Antibodies to ZP-2 or ZP-3 had no other adverse effect on in vivo or in vitro preimplantation development.