PIP: 10 men aged 30-48 were studied for autoimmune responses following bilateral vasectomy. During a period of up to 24 months lymphocytotoxic antibodies (LCA) against panels of normal lymphocytes developed in 6 men and against a panel of leukemia cells in 7. A few of the men also developed marked increases of antinuclear (ANA) and antismooth muscle (ASMA) antibodies. The surgical control cases showed no rise of LCA activity within a postoperative period of up to 1 year; the sera of 2/10 healthy hospital employees revealed an incidence of LCA activity similar to that reported in normal populations. The study showed that 60-70% of the vasectomized men developed LCA; an incidence similar to the 50-60% incidence reported with respect to sperm-agglutinating antibodies. Vasectomy in rats, mice, and guinea pigs elicited an antisperm antibody response in some strains but not in others. Apart from incidence there were also variations in the intensity of immune reaction, not only relative to LCA but also relative to antibody titers of ANA and ASMA. Since the immunologic and morphologic changes were observed only in a portion of those who were vasectomized and since the reactions varied in incidence and intensity among the subjects, it is suggested that immune response genes may be operative in the postvasectomy responses.