To assess the efficacy of methandrostenolone in the treatment of osteoporosis a 26-mo double-blind study was performed with 13 treated and 13 control (placebo) postmenopausal osteoporotic females. Drug effect was assessed primarily by determinations of total body calcium (TBC) by neutron activation analysis, essentially a measurement of total bone mineral mass. Results in the 16 patients completing the study (10 treated and 6 placebo), as well as in all 26 patients participating in the study, showed significant (p less than 0.01) differences in the change in TBC between treated and control groups. In patients dropping out, TBC changes through the time of dropout were similar to those in patients completing the study. In those patients completing the study, TBC increased 2% in the treated group and decreased 3% in the placebo group. An approximate sixfold difference in extraskeletal calcium balance would be required to explain the magnitude of the observed intergroup TBC difference. The drug effect appeared to persist throughout the 26-mo observation period. Thus these data strongly suggest that long-term use of methandrostenolone in postmenopausal osteoporosis prevented bone loss; the possibility that it increased bone mass above initial values is less certain.