Calcitriol was compared with placebo in the treatment of postmenopausal osteoporosis in a double-blind, randomized, parallel clinical trial of 24 months' duration. Adjustment was made in dietary calcium to maximize the dose of calcitriol. The study was completed by 15 patients who received placebo and 12 patients who received calcitriol. The calcitriol group had positive slopes (compared with negative slopes for the placebo group) for total body calcium, bone mineral content of the radius, bone mineral density of the lumbar spine, and radiographic absorptiometry of the middle phalanges. The difference between the two groups was statistically significant for each of these measurements. The fracture rate in the treatment group was 250 per 1,000 patient-years as compared with 333 for the placebo group. The mean dose of calcitriol was 0.8 micrograms per day. Hypercalcemia, hypercalciuria, and perhaps nephrolithiasis were observed as complications of treatment. Calcitriol increased bone mineral density by decreasing bone resorption, but not by increasing bone formation. Future studies should concentrate on treatment with oral calcitriol in lower doses. It would also be of interest to examine parenteral administration of calcitriol. It is possible that bone formation can be increased by achieving higher serum levels of the drug, whereas complications may be avoided by using a non-oral route of administration.