We studied 25-hydroxyvitamin D3 (25(OH)D3) metabolism and its effect on calcitriol metabolism in renal failure achieved by partial nephrectomy in rats. Metabolic clearance rates (MCRs) of 25(OH)D3 were significantly decreased in rats with renal failure (creatinine clearance, 0.21 +/- 0.02 ml/min/100 gm; MCR, 54.6 +/- 3.5 microliters/min/kg, n = 6) in comparison with normal control rats (creatinine clearance, 0.56 +/- 0.03 ml/min/100 gm; MCR, 73.4 +/- 1.6 microliters/min/kg, n = 5, both p less than 0.01). Because production rates (PRs) of 25(OH)D3 were not different between the two groups of rats (renal failure, 1.8 +/- 1.1; control, 1.8 +/- 0.42 microgram/kg/day), the decreased MCR resulted in elevation of plasma levels of 25(OH)D3 (22.7 +/- 1.6 vs control 17.1 +/- 0.28 ng/ml, p less than 0.01). Injection of 600 ng 25(OH)D3 per day for 6 days significantly increased the MCR of 25(OH)D3 in both normal rats (89.6 +/- 3.2 microliters/min/kg, n = 6, p less than 0.01) and rats with renal failure (84.9 +/- 9.7 microliters/min/kg, n = 6, p less than 0.01) when compared with normal rats (73.4 microliters/min/kg) and rats with renal failure (54.6 microliters/min/kg) injected with vehicle, respectively. To study the effect of 25(OH)D3 on calcitriol metabolism, MCRs of calcitriol were measured in normal rats and in rats with renal failure that received daily injection of 600 ng 25(OH)D3 for 6 days.(ABSTRACT TRUNCATED AT 250 WORDS)