We prospectively studied the long-term effects of intravenous calcitriol in 17 hemodialysis patients with severe secondary hyperparathyroidism (HPT) for 25.7 +/- 3.4 (+/- SE) months. Calcitriol was given thrice weekly after dialysis. Subsequently, changes were made every 3-4 weeks based upon serum chemistries. Total calcium and inorganic phosphorus were measured weekly; alkaline phosphatase (AP) and IRMA-PTH were measured monthly. Inorganic phosphate was controlled with calcium supplements. With calcitriol therapy both IRMA-PTH and AP decreased from 876 +/- 113 to 65 +/- 13 pg/ml (p < or = 0.001) and 432 +/- 106 to 103 +/- 15 U/ml (p < or = 0.001), respectively. Each patient had a reduction in IRMA-PTH and AP. Nadir IRMA-PTH occurred at 55.4 +/- 7.3 weeks. The maximum and mean maximum doses of calcitriol were 8.0 and 4.1 +/- 0.4 micrograms thrice weekly, respectively. Hypercalcemia tended to occur in those patients who were hypercalcemic prior to the initiation of intravenous calcitriol therapy. All hypercalcemic episodes were asymptomatic and reversed either by temporary withdrawal or lowering of the calcitriol dose. Hyperphosphatemia developed in those patients with a history of elevated serum phosphates and was mostly related to dietary and medication noncompliance. We conclude that intravenous calcitriol was uniformly effective and safe for the long-term therapy of severe HPT in ESRD. Careful attention to serum phosphate control is required.