Human patient sera containing antisperm antibodies (from vasectomized men and infertile women) immunologically react with the synthetic peptide P10G (PGGGTLPPSG), and affinity purified antibodies to P10G (anti-P10G) react with human spermatozoa (O'Rand et al., 1990). In this study P10G was used to elicit antibodies and the effect of the antibodies on fertility in female mice determined. The P10G sequence is derived from the 14-kDa rabbit sperm autoantigen, RSA (O'Rand and Widgren, 1990). The results of this study demonstrate that female mice can become infertile when immunized with the synthetic peptide P10G conjugated to the carrier protein keyhole limpet hemocyanin (KLH). However, the results also show that it is important to distinguish those mice with high serum antibody levels from those with lower levels. Infertility was clearly apparent in the high titer subgroup with an 80% decrease in pregnancy rate during the last of three matings and a 71% decrease in litter size over all three matings when compared to the low titer subgroup or the control groups. Significantly, mice immunized with P10G without carrier protein show no detectable antigen specific proliferation of lymph node cells in response to 100 microM of the peptide. P10G is not a T-cell epitope, but rather a B-cell epitope and it does not elicit an autoimmune response in the female mouse. This demonstration in mice is an important first step in the development of a safe human immunocontraceptive vaccine.