OBJECTIVE The mechanism of the beneficial effect of immunotherapy for human reproductive wastage remains to be elucidated. Because some women with unexplained recurrent spontaneous abortion are immunized with their partner's lymphocytes, it is important to determine whether such immunization results in elevation or enhancement of immunity to spermatozoa, because antigenic cross-reactivity between lymphocytes and spermatozoa has been reported. METHODS The present study was initiated to evaluate the changes in antisperm antibody titer and lymphocyte subsets after immunotherapy as compared to before immunotherapy. Antisperm antibody detection was performed by SpermCheck Assay, which is based on a modification of the immunobead test. Maternal lymphocyte subsets were analyzed in two-color flow-cytometric experiments. RESULTS The percentage of antibody-positive sperm decreased significantly (P = 0.0008) after immunotherapy. The percentage of B(CD19+) cells (P = 0.0003), cytotoxic T(CD8+ and CD11b-) cells (P = 0.02) and the Th/Ts ratio (P = 0.005) decreased significantly, while suppressor T(CD8+ and CD11b+) cells increased significantly (P = 0.0002) after the immunotherapy. This suggests that cell-mediated immunosuppression was induced by immunotherapy. CONCLUSIONS The data of the present study suggest that antisperm antibodies have potential for use as a marker for a deficiency in maternal genital tract immunosuppressor mechanisms and that immunotherapy could be an effective treatment for women with antisperm antibodies who have unexplained recurrent abortions.