Protection of spermatogenesis from cytotoxic drug-induced damage has been investigated in the rat. Complete germinal aplasia was observed at 8 and 11 weeks after four doses of procarbazine hydrochloride administered weekly (150 mg/kg, first dose; 100 mg/kg, 3 subsequent doses). Pretreatment of rats for 6 weeks plus continued treatment during procarbazine administration with testosterone enanthate, 240 micrograms/100 g body weight, resulted in a marked protection of spermatogenesis. A mean of 22% of seminiferous tubule cross-sections at both 8 and 11 weeks exhibited spermatogenesis, and developing spermatids were observed in 60% of these repopulating tubules at the later time. These results provide evidence that protection of spermatogenesis during chemotherapy may be achieved by androgen treatment.