Metabolic bone disease is common in children and adults with chronic cholestasis. We evaluated baseline vitamin D (vitamin D2 and D3), 25-OH vitamin D2 and D3, 1,25(OH)2 vitamin D, vitamin D-binding protein, bone mineral content and dietary mineral content in six children (mean age: 12.1 years) with cholestasis since infancy. Absorption of 25-OH vitamin D3 and vitamin D2 was evaluated by measuring serial serum concentrations after a test dose. Bone mineral content was reduced by greater than 2 S.D. in five of six subjects compared to age-specific controls; none had radiographic evidence of rickets but all had osteopenia. Dietary Ca and P content in the subjects was comparable to the recommended daily allowance for age-specific children. Baseline serum vitamin D2 concentrations were undetectable in all but one cholestatic subject despite oral supplementation with 2,500 to 50,000 IU per day vitamin D2. Baseline serum 25-OH vitamin D was 33.2 +/- 6.0 ng per ml (mean +/- S.E.) and comparable to our laboratory norms (15 to 50 ng per ml). Serum 1,25(OH)2 vitamin D and "free" 1,25(OH)2 vitamin D were both significantly (p less than 0.05) reduced compared to controls. A significantly blunted rise and reduced area under the absorption curve (both p less than 0.001) after 1,000 IU per kg vitamin D2 was found in cholestatic children (0.8 ng +/- 0.5 ng per ml and 18.0 +/- 14.3 ng hr per ml, respectively) compared to controls (59.5 +/- 10.0 ng per ml and 1,780 +/- 253 ng hr per ml, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)