Acute leukemia frequently presents with skeletal symptoms; however, the etiologies of bone pain and osteopenia are poorly understood. We present the case of an adolescent girl with acute leukemia who developed vertebral fractures after being in complete remission for 3 months. Bone mineral density was very low (less than 0.6 g/cm2) but remained stable during the subsequent 3 months despite continuation therapy with methotrexate and prednisone. Findings of a bone biopsy were consistent with a recent episode of aggressive bone resorption. We suggest that paracrine secretion of lymphokines may mediate loss of bone mass during the active phase of acute leukemia, although clinical bone disease may not develop until after complete remission is achieved.