Spermatogenesis in a melanoma patient treated with 12 courses of acridinyl anisidide (AMSA) (20 mg/m2/course) was studied by monitoring sperm concentration, motility, and morphology at various phases of treatment. Chemotherapy was interrupted for 20 weeks between the ninth and tenth course. Sperm concentration and motility began to decline after the second course. At the third course, the percentage of morphologic abnormalities had increased to 86.5% from a pretreatment value of 57.8% (P less than 0.001). Azoospermia was observed at the sixth course and persisted until 12 weeks after the ninth course, when semen levels returned to pretreatment levels: 20 million/ml; 70% motility; 60.1% abnormal forms. Three weeks after the 12th course, the sperm count was reduced to 250,000/ml, motility to 5%, and abnormalities increased to 84.0%. The rapid recovery of normal spermatogenesis observed during the chemotherapy interruption indicates that AMSA has only a temporary, reversible effect on differentiating germinal cells with no toxicity to stem cells.