We investigated the effects of epididymo-orchitis and ciprofloxacin on rat testicular histology and spermatogenesis. The control group underwent left orchiectomy. The second group received oral ciprofloxacin (150 mg/kg/day) for 10 days. Escherichia coli (10(6) cfu/mL, 0.1 mL) was injected into the proximal right ductus deferens in the third group. The fourth group received ciprofloxacin treatment 48 h after E. coli inoculation. In groups 3 and 4, bilateral orchiectomy was performed 14 days after the challenge. In healthy rats, ciprofloxacin caused recognizable histological damage associated with a mild decrease in testicular volume and sperm concentration. Infected testicles in groups 3 and 4 revealed severe histological damage associated with severe testicular atrophy and impaired spermatogenesis that were more significant in infected rats which received ciprofloxacin treatment. Contralateral testicles in these animals showed similar histopathological changes to a lesser extent. The results of our study suggest a gonadotoxic potential for ciprofloxacin and this potential in humans should be addressed with further studies.