After at least four courses of intermittent chemotherapy, 14 of the 15 men with malignant lymphoma had elevated serum follicle-stimulating hormone (FSH). In three of these subjects, serial studies showed progressive increases in basal FSH and exaggerated FSH responses to luteinizing hormone releasing hormone (LHRH). Although gonadal biopsies were not done, this elevation of FSH is indicative of progressive and severe damage to the germinal epithelium by chemotherapy. Elevated leutinizing hormone (LH) was found in seven and decreased testosterone (T) in two of these subjects. Increased LH responses to LHRH stimulation were also found in the three subjects studied. These findings suggest that the testicular damage is not restricted to the germinal tissue. In four male subjects with acute myeloid leukemia treated by intermittent chemotherapy not containing any alkylating agents, FSH, LH, and T levels were normal. Three of the 4 female patients with malignant lymphoma and two with acute myeloid leukemia had normal basal, serial, and LHRH-stimulated FSH, LH, and estradiol (E2) levels. Elevated gonadotropins and low E2 were found only in subjects who had received abdominal irradiation.