Primary hyperparathyroidism (HPTH) is a known risk factor for cortical bone loss. The primary objective of this study was to examine the time course and location of changes in bone mass within the first year after parathyroidectomy (PAX). The secondary goal was to evaluate the efficacy of combined estrogen therapy and parathyroidectomy in postmenopausal women. Thirty-two subjects with primary HPTH participated in a prospective, longitudinal study for at least 1 yr. Twenty-seven subjects underwent PTX, while five received no therapy (control). Among the PTX patients, 21 were postmenopausal women, and 8 of these women also received estrogen. Subjects had serial measurements of parathyroid hormone levels, serum chemistries, and bone density at multiple sites. Among all PTX patients, lumbar spine, hip, and whole body bone mineral content increased significantly (3.8-6%; p < 0.005) at 12 mo, with most of the increments observed by 3 mo. In postmenopausal women, estrogen treatment resulted in higher increments in the femoral neck (8.6 +/- 2% vs 4.9 +/- 1.2%, respectively; p = 0.07) and the whole body (6 +/- 2% vs 2.4 +/- 1.6%, respectively; p = 0.07). In HPTH, early and generalized increments in bone mass follow PTX, and the combination of surgery with estrogen therapy may be superior to surgery without estrogen treatment. A randomized, controlled trial including PTX, estrogen, and a combination of the two is needed to determine the optimal therapy in postmenopausal women.