We investigated the effects of GH on bone structure and turnover by histomorphometry in GH-deficient adults. Therefore, transiliac bone biopsies were obtained before and after 1 yr of treatment in 36 GH-deficient men (mean age, 28 +/- 4 yr). Thirteen patients had isolated GH deficiency and 23 patients had multiple pituitary hormone deficiencies. Patients were randomly assigned to four treatment groups. Groups 1, 2, and 3 received 1, 2, and 3 IU/m2/day (0.35, 0.69, and 1.3 mg/m2/day) [corrected] GH, respectively, and the fourth group received placebo for the first 6 months and 2 IU/m2/day (5.8 mg/m2/day) GH for the subsequent 6 months. GH treatment resulted in an increase of cortical thickness from 0.98 +/- 0.27 to 1.20 +/- 0.35 mm (P = 0.005), but trabecular bone volume did not change. Bone formation variables increased significantly: osteoid surface increased from 8.5 +/- 5.3 to 15.5 +/- 6.1% (P = 0.0002), mineralizing surface increased from 6.7 +/- 2.5 to 10.8 +/- 4.4% (P = 0.0002), and bone formation rate increased from 0.04 +/- 0.02 to 0.08 +/- 0.04 mm3/mm2/day (P = 0.0001). Eroded surface did not change, but osteoclast number increased from 0.6 +/- 0.5 to 1.25 +/- 0.5 Oc/mm2 (P = 0.0001). The relative formation period increased significantly (P = 0.001), whereas the resorption period, including reversal phase, decreased from 65 to 40 days (P = 0.02). Activation frequency increased from 0.39 +/- 0.17 to 0.74 +/- 0.34 y(-1) (P = 0.0001). These data indicate a stimulated bone turnover as a result of GH treatment and a shorter resorption and reversal time. The increased turnover did not result in an increased trabecular bone volume, but the cortical thickness increased significantly.