In many patients with involutional osteoporosis anabolic steroids may produce a rapid subjective improvement and a pronounced reduction in the frequency of complaints. Animal experiments have demonstrated that anabolic steroids can also have an objective effect on bone tissue. Twenty (20) post-menopausal osteoporotic patients were randomly assigned to 2 different treatment regimens; 10 patients were treated with 50 mg i.m. of nandrolone decanoate (ND) every 3 wk for 12 mth and 10 patients were treated with a placebo. Both groups also received an oral calcium supplement (1 g/day). Bone mineral content (BMC) was measured by dual photon absorptiometry before and after 1, 3, 6 and 12 mth of treatment. Plasma alkaline phosphatase (ALP) and urinary hydroxyproline excretion were measured at the same time. Intestinal calcium absorption was measured by the 47Ca oral test before and after treatment. A transiliac bone biopsy was performed before and after treatment in 4 patients in each group. After 1 yr there was a significant increase in lumbar spine BMC in the group receiving calcium plus ND. A progressive increase in plasma ALP was also observed in the group treated with ND but this was not significant, whereas radiocalcium absorption did increase significantly in this group. Histomorphometric study of bone samples demonstrated a significant increase in trabecular bone volume (TBV) and in active osteoid surface area in the patients treated with ND. Because plasma ALP tends to increase when a small decrease in bone resorption occurs (as measured by urinary hydroxyproline excretion) and the active osteoid surfaces also significant augment, we concluded that ND therapy increases the bone formation rate through inhibition of bone resorption. This interpretation could explain the considerable increase in lumbar spine BMC and the significant increase in TBV observed in patients treated with ND.