Patients with testicular cancer treated with cisplatin can undergo feminization that is understood poorly. Rat model studies recently showed that cisplatin can feminize in part the profile of hepatic steroid-metabolizing enzymes and circulating hormone levels. This study was undertaken to determine whether cisplatin similarly might contribute to the perturbations in gonadotropin or steroid hormone levels that can occur in patients undergoing cisplatin-based treatment for testicular cancer. Analysis of serum free testosterone, total testosterone, and androstenedione levels revealed that these hormones were not altered significantly in patients during a 38-week period of cisplatin-based treatment and follow-up. Estradiol levels were elevated before chemotherapy and were reduced to normal levels during treatment. This reduction was attributed to the cytotoxic effect of chemotherapy on the tumors and the resultant reduction in serum chorionic gonadotropin levels. Serum dihydrotestosterone (DHT) levels were normal before chemotherapy but progressively became elevated during treatment with cisplatin in five of ten patients examined. The rise in DHT may relate to the previously described increase in hepatic androgen 5 alpha-reductase activity in cisplatin-treated rats. Levels of the gonadotropins, luteinizing hormone, and follicle-stimulating hormone (FSH) were normal before cisplatin-based treatment was administered; however, FSH was elevated selectively during chemotherapy. This selective induction of FSH may reflect an effect of cisplatin on the hypothalamic secretion of gonadotropin-releasing hormone. Taken together, these findings suggest that cisplatin contributes to the perturbation of steroid and peptide hormone levels in patients with testicular cancer and perhaps in others undergoing cisplatin-based chemotherapy.