This investigation was conducted to evaluate whether or not experimentally produced epididymitis could induce the development of cytotoxic sperm antibodies and if effective antibiotic therapy could reverse the development of immunity to sperm. Escherichia coli was injected into the tail of the epididymis in adult Lewis rats to induce epididymitis and was allowed to incubate for 24 h, 72 h, 8 days, or 15 days. Serum titers of cytotoxic sperm antibodies at these time intervals were determined. Sperm antibody titers began to rise 3 days after inoculation, peaked, and plateaued at 8 days. The titers were negligible in the control rats. Two other groups of rats were inoculated with E. coli in a similar manner and were treated with tetracycline 25 mg/kg/day starting at either 24 h or 8 days after inoculation, for 7 days. The antibody titers became negligible in these two treated groups, the results being statistically significant when contrasted with the infected but untreated groups (p < .001 and < .05, respectively, for the 24-h and 8-day groups). However, histological examination of the antibiotic-treated and untreated specimens revealed significant inflammation and infection of the epididymis in both treated groups. Testicular alterations were consistent in both groups. It is concluded that epididymitis consequent to infection with E. coli can induce cytotoxic antibody formation in Lewis rats. Treatment with appropriate antibiotics may suppress the antibody response either through a direct immunosuppressive effect of the antibiotic or through a decrease in the antigenic load of killed sperm secondary to eradication of the infection.