ABSTRACT: To test the hypothesis that intraperitoneal insemination of sperm induces the expression of anti-sperm antibodies a prospective study was designed. Fifteen women undergoing intraperitoneal insemination (with or without oocyte transfer) were studied with 11 women having evaluation of anti-serm antibodies. Sperm antibodies were detected by the immunobead test prior to intraperitoneal insemination and after each treatment cycle. Two criteria were used to assess positivity: the first based upon negative controls and the second based upon the evaluation of 20 fertile control couples. Using the first criteria, of 11 of the women undergoing IPI for the first time, 7 were initially negative and 4 were initially positive for at least 1 isotype. After treatment, 3 additional patients were positive (for a total of 7) and 4 patients remained negative. This alteration in sperm antibody frequency was not different (P = .4) as determined by the Fisher's Exact Test. Four of the 11 patients underwent a second cycle of IPI. All 4 patients were negative prior to the first treatment and 3 were negative prior to the second treatment. Subsequent to the second exposure, all 4 of these women were positive for at least 1 isotype. This shift in frequency distribution after 2 cycles was significant (P = .01). The frequency of antisperm antibodies for the same 11 patients was evaluated by using fertile control values as the basis of positivity. Two patients (18%) were positive for anti-sperm antibodies prior to intraperitoneal insemination. There was no change in the frequency of positivity after 1 cycle of IPI. After 2 cycles of IPI 1 patient previously shown to be negative for anti-sperm antibodies was subsequently positive. This shift in frequency was not significant (P = 0.1).