Although most patients with postmenopausal osteoporosis have normal or low values for serum immunoreactive parathyroid hormone (iPTH), we have reported previously that a small subset (about 10% of the total group) have increased values. We studied three patients representative of this latter group. Serum iPTH was two to three times higher than the age-adjusted normal mean, serum ionized calcium and total calcium were in the lower half of the normal range, and serum 1,25-dihydroxyvitamin D [1,25(OH)2D] was in the low-normal range. Six months of treatment of one patient with 0.5 microgram/day of synthetic 1,25(OH)2D improved calcium absorption and balance; however, serum iPTH remained high. After surgical removal of 1,010 mg of hyperplastic parathyroid tissue, serum iPTH decreased to normal. These and other data suggest that increased serum iPTH in these patients was caused by secondary hyperparathyroidism, possibly because of inadequate conversion of 25-OH-D to 1,25(OH)2D.