A prospective study was conducted to investigate the possibility of osteoporosis after treatment for childhood acute lymphoblastic leukemia (ALL). Forty-two survivors of ALL had the trabecular bone density of the spine evaluated by quantitative computed tomography, 6 to 98 months (mean 42 months) after completion of chemotherapy. The ALL survivors had significantly lower bone density than age-, gender-, and race-matched nonleukemic control subjects had (10% less, p less than 0.001); this decrease was accounted for solely by the subset of patients who had received cranial irradiation (n = 30; p less than 0.001). The relative reduction in bone density in ALL survivors was unrelated to age at the time of diagnosis or time without therapy. The effects on bone density of 18 Gy and of 22.5 to 25.2 Gy were indistinguishable. We conclude that survivors of ALL commonly have reduced bone density in the lumbar spine and suggest that the diminution is related to nervous system irradiation, not to the disease or to chemotherapy.