This study was designed to assess the effects of smoking on bone mass and bone loss and to ascertain whether these effects are independent of effects on adiposity and hormone concentrations. A total of 84 healthy, peri- and postmenopausal women were studied prospectively over 3 1/2 years. Heavy smokers had significantly (p less than 0.05) lower radial and vertebral bone mineral content than light or nonsmokers (who did not differ from each other). In regression models, which contained measurements of obesity, pack-years smoking remained a significant predictor of bone mass. However, there were no detectable effects of smoking on rates of bone loss at any site. Smokers appear to be at greater risk of osteoporosis due to their lower bone mass. However, this reduced bone mass is already present around the time of menopause, and rates of bone loss during this period do not appear to be influenced by smoking. Furthermore, we have previously shown in this population that menopausal serum estrogen concentrations (which determine rates of bone loss) do not differ between the smokers and nonsmokers. Further studies of larger groups are required to determine whether small differences in bone loss may exist, since the power to detect such differences was not ideal in this study.