Vitamin D metabolites were measured in children, untreated with glucocorticoids, who had renal disease. Two groups were defined in relation to endogenous creatinine clearance values: those with impaired clearance , 0 to 48 ml/min per 1.73 m2; and those with unimpaired clearance, 75 to 150 ml/min per 1.73 m2. Serum 1.25(OH)2D was 16 +/- (SD) 12 pg/ml in impaired patients (N=24) and 48 +/- 16 pg/ml in unimpaired patients (N=18). The latter level is not different from healthy childhood controls (43 +/- 12 pg/ml; N=194). Serum samples of 25(OH)D2 and D3 were comparable in each group and not different from control values of 33.2 +/- 10.3 ng/ml. Serum 24,25(OH)2D was 0.6 +/- (SD) 0.14 ng/ml in patients with a clearance of less than 13 ml/min per 1.73 m2, 1.39 +/- 0.54 ng/ml in those with a clearance of 18 to 48 ml/min per 1.73 m2, and 152 +/- 0.91 ng/ml in patients without an impairment of clearance. Only patients with the lowest clearance had values different from control values of 1.70 +/- 0.57 ng/ml. In our study we suggest that a significant reduction in 24,25(OH)2D and 1,25(OH)2D are found at low clearance values in children with tubulointerstitial disease. Our study further suggests that a reduction in renal tubular mass is important in accounting for these changes in vitamin D metabolite values.