Calcitriol lowers serum parathyroid hormone (PTH) levels in patients with secondary hyperparathyroidism, but its effect on calcium-regulated PTH release remains controversial. Thus 11 patients with secondary hyperparathyroidism underwent dynamic tests of parathyroid function before and after 4 mo of intermittent calcitriol therapy. Serum calcitriol levels rose from 8 +/- 1 to 55 +/- 9 (SE) pg/ml, P < 0.01, serum total and ionized calcium levels increased, and serum PTH levels decreased from 584 +/- 154 to 154 +/- 31 pg/ml, P < 0.05. The maximum increase in serum PTH during hypocalcemia did not differ before (248 +/- 78 pg/ml) or after (280 +/- 100 pg/ml) treatment, but the increase in PTH, expressed as a percentage of preinfusion values, was greater after treatment (329 +/- 73 vs. 132 +/- 10%, P < 0.05). The decreases in serum PTH during calcium infusions did not differ before (70 +/- 5%) or after (73 +/- 5%) therapy, and the set point for PTH release did not change (1.20 +/- 0.03 vs. 1.23 +/- 0.01 mmol/l, not significant). Calcitriol modifies PTH secretion during hypocalcemia in secondary hyperparathyroidism without affecting the set point for PTH release; although calcitriol lowers serum PTH levels, it may also restore the secretory reserve of hyperplastic parathyroid tissues during hypocalcemia.