Osteopenia is a frequent complication of anorexia nervosa (AN). To determine whether the deficit in bone mineral changes during the course of this illness, we studied 15 adolescent patients prospectively for 12-16 months using dual photon absorptiometry of the spine and whole body. At follow-up, mean weight, height, and body mass index (BMI) had increased significantly, although 6 girls had further weight loss or minimal gain (less than 1.2 kg). Spontaneous menses occurred in 2 girls, and 3 others were given estrogen replacement. Bone mineral density of the lumbar spine did not change significantly (mean +/- SD, 0.836 +/- 0.137 vs. 0.855 +/- 0.096 g/cm2), while whole body bone mineral density increased (0.710 +/- 0.118 vs. 0.773 +/- 0.105; P less than 0.05). Despite gains in bone mineral, 8 patients had osteopenia of the spine and/or whole body. Changes in weight, height, and BMI were significant predictors of change in bone mineral density. Increased bone mass occurred with weight gain before return of menses; conversely, weight loss was associated with further decreases in bone density. In 1 patient who failed to gain weight, estrogen therapy resulted in increased spinal, but not whole body, bone mineral. We also studied a second group of 9 women who had recovered from AN during adolescence. All 9 had normal whole body bone mineral for age, but 3 had osteopenia of the lumbar spine. We conclude that osteopenia in adolescents with AN reflects bone loss, perhaps combined with decreased bone accretion. Weight rehabilitation results in increased bone mineral before the return of menses. Estrogen may have an independent effect on bone mass. The persistence of osteopenia after recovery indicates that deficits in bone mineral acquired during adolescence may not be completely reversible.