We evaluated whether calcitriol administration to healthy men stimulates bone resorption. We compared serum 1,25-(OH)2-D concentrations, Ca and PO4 balances, and urinary hydroxyproline excretion rates in four healthy men adapted to a low Ca diet providing only 4.0 +/- 0.2 SD mmoles Ca/day to those in four healthy men eating a comparable diet (4.2 +/- 0.9 mmoles Ca/day) during the chronic oral administration of calcitriol, 0.75 micrograms every 6 hr. Serum 1,25-(OH)2-D levels averaged 94 +/- 16 pM during the control studies and 209 +/- 35 pM during calcitriol administration. Net intestinal Ca absorption averaged 0.5 +/- 0.3 mmoles/day during control and 1.8 +/- 0.5 mmoles/day during calcitriol (P less than 0.005), but urinary Ca excretion averaged 8.7 +/- 2.0 mmoles/day during calcitriol as compared to 2.9 +/- 1.4 mmoles/day during control (P less than 0.005). Thus, mean Ca balance, which averaged -2.4 +/- 1.2 mmoles/day during control, was more negative during calcitriol at -6.3 +/- 2.4 mmoles/day (P less than 0.05). Average daily PO4 balances averaged +7.7 +/- 1.5 mmoles/day during control but only tended to be negative during calcitriol at -1.1 +/- 5.4 mmoles/day, (NS). Urinary hydroxyproline excretion averaged 0.26 +/- 0.03 mmoles/day during control and 0.49 +/- 0.06 during calcitriol (P less than 0.001). We conclude that elevated serum 1,25-(OH)2-D concentrations in healthy men eating low Ca diets stimulate bone resorption.