Analysis of semen from 16 patients treated with cyclophosphamide for nephrotic syndrome showed azoospermia in three and oligospermia in seven. Analysis was normal in the other six. Prolonged treatment, particularly with larger total dosage, was associated with a higher incidence of gonadal dysfunction. Recovery was not evident at follow-up, 2 years and 9 months to 9 years and 1 month after cessation of the therapy. Limitation of treatment with cyclophosphamide to 8 weeks/course (2.5 mg/kg/day) minimizes this side effect without greatly increasing the rate of relapse of the nephrotic syndrome in the first 2 years after therapy.