This double-blind, placebo-controlled study was undertaken to determine 1) the efficacy of oral risedronate for prevention of bone loss in healthy, early postmenopausal patients with normal bone mass, 2) the effect on bone mass when treatment was stopped, and 3) the safety and tolerance of risedronate in this population. A group of 111 patients were randomized to oral placebo, risedronate 5 mg daily, or risedronate 5 mg cyclically, for 2 yr followed by 1 yr off treatment. Measurements included percentage change from baseline in lumbar spine bone mineral density (BMD) at 24 months; percentage change from baseline in BMD of the femoral neck, trochanteric region, and Ward's triangle region of the proximal femur; and changes in biochemical markers of bone turnover. After 2 yr, there was a mean increase in BMD of the lumbar spine of 1.4% from baseline and of 5.7% vs. placebo in the risedronate 5 mg daily group. There were decreases from baseline in BMD of 1.6% and 4.3% in the risedronate 5 mg cyclic and placebo groups, respectively. By the end of 24 months, trochanteric bone mass at the hip increased by 5.4% in the risedronate 5 mg daily group and by 3.3% in the risedronate 5 mg cyclic group vs. placebo. Bone mass was maintained at the femoral neck in the 2 active-treatment groups vs. a 2.4% mean loss with placebo. During the treatment-free follow-up, bone turnover increased toward baseline in both risedronate groups. By the end of that year, lumbar spine bone mass in all 3 groups was lower than at baseline. Oral risedronate was well tolerated. We conclude that risedronate (5 mg daily) increases bone mass and risedronate (5 mg cyclic) appears to prevent bone loss in early postmenopausal women with normal BMD.