The authors present the results of study of testicular spermatogenetic and endocrine function in adult males treated with high doses of cyclophosphamide for nephrotic syndrome during childhood and/or adolescence. Seventeen males, mean age of 22.5 years (range, 17-30) were examined after mean follow-up of 11.8 (5-17.3) years. Mean age at the time of treatment was 10.8 (3.6-17.6) years; mean duration of cyclophosphamide treatment was 240 (39-701) days, and mean total cumulative doses were 641 mg/kg body weight (103-1999) or 16.4 (3.9-55.7) grams. All the patients undergone normal pubertal development and had normal sexual characteristics. Eleven were normospermic (more than 20 x 10(6)/ml spermatozoa), one oligospermic and five azoospermic. There was a significant inverse correlations of sperm density with cyclophosphamide dosage and duration of treatment. These variables seem to be more important for cyclophosphamide toxicity, than stage of sexual development at time of treatment. Raised basal and stimulated FSH concentrations in oligoazoospermic patients were in keeping with impaired spermatogenesis. These patients had also raised basal and stimulated LH concentrations suggesting compensated Leydig cell failure. Subgroup of normospermic patients with lower spermatozoa concentrations (20-40 x 10(6)/ml) had significantly raised FSH and LH responses on stimulation with gonadotropin releasing hormone, suggesting dysfunction both tubular and interstitial cell component of the testis. In other normospermic patients gonadotropin responses were not different from controls. Basal and HCG stimulated testosterone concentrations showed no differences between patients and controls. These results confirmed significant inverse correlations of cyclophosphamide dosage with its effect on spermatogenesis, and documented the long-term effect on the Leydig cell function requiring further follow-up.