There is only limited information on gonadal function after bone marrow transplant (BMT) during childhood. The existing data is based primarily on the use of single dose or fractionated total body irradiation (TBI). In the present study, we evaluated gonadal function in 33 patients (18 females, 15 males with ALL, n = 18 and AML, n=15), treated with hyperlractionaled TBI before puberty. Median age at diagnosis was 4.8 years (0.4-11.2 yrs), median age at BMT was 7.3 years (3.8-11.5 yrs) and median age at last evaluation of gonadal function was 17.1 years (9.3-22 yrs). Transplant cytoreduction consisted of hyperfractionated TBI (125 cGy TID for total dose of 1375 to 1500 cGy) and 120 mg/kg of Cytoxan; male patients received an additional 400 cGy testicular boost. Fifteen of 33 patients had received cranial irradiation as part of previous treatment of their underlying disease (1000-2400 cGy) but none of the males had received testicular irradiation. Five of 15 boys had elevated baseline LH, 9 of 15 had elevated baseline FSH, and 2 of 15 had elevated LH and low testosterone requiring testosterone treatment to complete pubertal development. Fourteen of 18 females had elevated baseline levels of LH and/or FSH; nevertheless, 8 females experienced spontaneous menarche at a mean age of 12.7 years (9.4-15.8 yrs). All 8 patients including 4 with elevated LH/FSH have regular menses. One female presented with precocious puberty. Eight of 18 females have required hormone replacement therapy. In conclusion, our data suggests hyperfractionated TBI results in preservation of Leydig cell function in males, while the incidence of germ cell dysfunction in males and ovarian failure in females appears to be similar to that reported after single dose or fractionated TBI.