Tumor necrosis factor alpha, the cytokine that participates in the autocrine growth control of hairy cell leukemia has strong bone resorptive properties. This prompted us to look for bone involvement in HCL. Bone mineral density (BMD) was not decreased in 14 HCL patients who did not have radiographic evidence of bone destruction. Osteopenia was found in only two HCL patients with skeletal complications of the disease and bone pain preceded diagnosis in both cases. Lymphomatous infiltration of the vertebral bodies T 12/L1 was confirmed histologically in the female patient while bilateral necrosis of the femoral head preceded the diagnosis of HCL in the male patient. Histomorphometry of bone biopsy samples was performed in another 12, previously untreated male HCL patients. Trabecular bone volume was found to be reduced in 11, greatly reduced in 5 of them, while osteosclerosis was found in only one patient. The increase of trabecular bone pattern factor, a new parameter for simple quantification of trabecular interconnection indicated a poorly connected trabecular lattice in eight of these 12 patients.