Severe hypercalcemia (serum calcium, 4.25-5.25 mmol/l), in association with osteolytic bone lesions, was found in a girl aged 2 yr 7 mo with common acute lymphoblastic leukemia (ALL). Hormonal studies excluded the possibility of the hypercalcemia being caused by primary hyperparathyroidism or ectopic parathyroid hormone secretion. Increased plasma prostaglandin E2 (PGE2) levels (130 ng/l), probably produced by leukemic cells, were considered to be one of the pathogenic mechanisms responsible for the occurrence of hypercalcemia in this patient. Both the hypercalcemia and the abnormal plasma PGE2 level returned to normal after chemotherapy.