To ascertain the impact of therapy on gonadal function and reproductive outcome among children treated for Hodgkin's disease, we reviewed the experience at Stanford University Medical Center during the years 1965-1986. There were 240 children 15 years of age or younger, 92 girls and 148 boys; with median follow-up of 9 years, maximum follow-up was 26 years. Of this cohort, data on gonadal function were available on 20 boys, 5 of whom were considered prepubescent; they had no clinical evidence of sexual maturation and were less than 13 years of age. Evaluation of the boys included testicular biopsy, semen analyses and the ability to procreate. Serum gonadotropin hormone levels (FSH, LH) were studied in 11 boys who also had semen analyses. Sexual maturation was attained in all boys without the need for androgen replacement. Among the eight boys treated with radiation alone, four were able to father a child (3 following 40-45 Gy pelvic radiation dose, 1 without pelvic radiation) from 3-19 years following treatment. Three others who received 30-44 Gy pelvic radiation were oligospermic when tested at 10 to 15 years post-treatment. Semen analyses in 10 of 12 (83%) boys who had been treated with six cycles of MOPP with or without pelvic radiation revealed absolute azoospermia with no evidence of recovery as along as 11 years of follow-up. Following prolonged azoospermia, 2 of the 12 boys (17%) had recovery of fertility, with normalization of sperm count and/or ability to procreate at 12 and 15 years following treatment. There was no correlation with serum gonadotropin levels and sterility. Data on menstrual history, pregnancy and offspring were available in 86 (92%) of the girls. Seventy-five of the 86 girls (87%) have normal menstrual function. However, none of the females who underwent pelvic radiation without prior oophoropexy has maintained ovarian function. Both the prepubescent and postpubescent boys were affected by 6 cycles of MOPP whether or not pelvic radiation was administered. On the other hand, in girls similarly treated, ovarian injury was directly related to both the number of cycles of chemotherapy and the ovarian radiation dose. The chances of maintaining gonadal function following combined modality treatment are significantly greater among girls than boys. The progeny of patients treated for Hodgkin's disease appear normal and no excess fetal wastage has been noted.