Testicular function of 17 males treated in childhood or adolescence for nephrotic syndrome (NS) with cyclophosphamide (CY) for a mean time of 240 days (mean total dosage of 16.4 g or 641 mg/kg body weight) was evaluated at a mean time of 11.8 years after treatment. Five were azoospermic, 1 oligospermic, and 11 normospermic. There was a significant inverse correlation of sperm density with CY dosage and duration of treatment. All patients had undergone normal pubertal development and had normal sexual characteristics. Both basal and gonadotropin-releasing hormone-stimulated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations were significantly raised in oligo- and azoospermic patients. Raised basal and peak FSH and LH concentrations in normospermic patients with a sperm count of less than 40 x 10(6)/ml were in keeping with impairment of two testicular components. However, mean basal plasma testosterone levels and mean peak plasma testosterone responses to human chorionic gonadotropin (HCG) did not differ significantly between patients and controls. Although LH responses to gonadotropin-releasing hormone suggested compensated Leydig cell failure in patients with testicular tubular damage, secretory reserve capacity of these cells, estimated by a HCG stimulation test, was preserved. Further follow-up is required to ascertain whether in these patients Leydig cell failure will develop with time.