Exercise is recommended as a means of preventing osteoporosis. When intensive, weight-bearing exercise is often associated with hypogonadism. As weight-bearing exercise is likely to be more beneficial at weight-bearing than nonweight-bearing sites, and hypogonadism is likely to be more detrimental to trabecular than cortical bone, we tested the hypothesis that exercise and hypogonadism result in differing regional effects: net benefits at weight-bearing, predominantly cortical sites, and net deficits at nonweight-bearing trabecular-rich sites. Bone density (grams per cm2), body fat, and fat-free mass (kilograms) were measured using dual x-ray absorptiometry in 44 ballet dancers, aged 17.0 +/- 0.2 yr (mean +/- SEM), 18 sedentary amenorrheic girls with anorexia nervosa, and 23 girls of comparable age with regular menstrual cycles. Bone density, expressed as a percentage above or below the mean in the girls with regular menstrual cycles, was normal or elevated at weight-bearing sites in dancers [femoral neck, 3.1 +/- 1.7% (P = NS); Wards triangle, 4.1 +/- 2.3% (P = NS); trochanter, 5.9 +/- 1.9% (P < 0.05)] and normal or reduced at these sites in girls with anorexia nervosa [-10.5 +/- 3.8% (P < 0.05), -7.8 +/- 4.3% (P = NS), and -8.7 +/- 4.0% (P < 0.05), respectively]. By contrast, deficits similar to those in girls with anorexia nervosa were found in dancers at nonweight-bearing sites [ribs, -5.7 +/- 0.8% (P < 0.01); arms, -4.6 +/- 1.1% (P < 0.01); skull, -5.9 +/- 1.3% (P < 0.01)] before, but not after, correcting for fat mass. Fat mass was 7.8 +/- 0.4 kg in dancers, similar to that in girls with anorexia nervosa (6.3 +/- 0.7 kg) and lower than that in girls with regular menstrual cycles (16.8 +/- 1.6 kg; P < 0.01). The net result of vigorous exercise, hypogonadism, and leanness in athletic amenorrhea may not be generalized osteoporosis. Weight-bearing exercise may offset the effects of hypogonadism at predominantly cortical weight-bearing sites, such as the proximal femur. Non-weight-bearing sites and weight-bearing sites containing substantial amounts of trabecular bone, such as the lumbar spine, may be adversely affected by hypogonadism while benefiting little from weight-bearing exercise. Deficits at nonweight-bearing sites may be attenuated by maintenance of body weight.