The effect of procarbazine, an antineoplastic drug, on the reproductive system of male Syrian hamsters was studied. Exposure to procarbazine (5 daily doses ranging from 20 to 500 mg/kg body weight) resulted in 5‐ to 7.5‐fold increase in sperm abnormalities, diminished sperm counts, and smaller testes within 4 wk. Transmission electron micrographs showed severe damage to the acrosomal plasma membrane and nucleus of the sperm head in treated hamsters. These findings corroborate the detrimental effect of procarbazine on the germinal tissue and strengthen the basis for using the sperm morphology assay for the detection of mutagens and possibly other germ‐cell toxicants in an in vivo mammalian system.