To measure the effect of testosterone replacement and venesection on spinal and peripheral bone mineral we prospectively studied six hypogonadal men and six eugonadal men with idiopathic hemochromatosis for 24 months. Venesections were performed every week on all patients, and intramuscular injections of testosterone were administered every 3 weeks to the hypogonadal men only. Bone mineral was measured by quantitative computed tomography in the spine and by single-photon absorptiometry in the forearm. During the 24 month period of observation serum testosterone concentrations and serum ferritin levels became normal. In the hypogonadal men mean lumbar spine bone mineral increased by 13.1 +/- 4.9% (95% CI, 0.5-25.6) and mean forearm bone mineral increased by 4.7 +/- 3.8% (95% CI, -5.1 to 14.6). In contrast in the eugonadal men treated over the same period, mean lumbar spine bone mineral decreased by 3.5 +/- 2.8% (95% CI, -10.9 to 3.8, P less than 0.01) and mean forearm bone mineral remained virtually unchanged (0.07 +/- 0.9%; 95% CI, -1.7 to 3.1, P less than 0.05). These data suggest that bone mineral increases in the lumbar spine and in the forearm in hypogonadal men with hemochromatosis treated by testosterone replacement and venesection.