A B S T R A C T The effects of vitamin D, 2.5 mg (100,000 U)/d for 4 d, on serum calcium, serum 25-hydroxyvitamin D (25-OHD), and serum 1a,25-dihydroxyvitamin D [la,25(OH)2D] were compared in 17 normal subjects and 6 patients with sarcoidosis who had normocalcemia and no history of hypercalcemia. The diagnosis was confirmed histologically in each of them. Vitamin D increased mean serum 25-OHD from 30±4 to 99±15 nglml (P < 0.001) and did not change mean serum 1a,25(OH)2D (32±3 vs. 29±3 pg/ml) or mean serum calcium (9.5±0.1 vs. 9.6±0.1 mg/dl) in the normal subjects. In contrast, vitamin D increased mean serum 25-OHD from 19±3 to 65±19 ng/ml (p < 0.05), increased mean serum la,25(OH)2D threefold from 40±7 to 120±24 pg/ml, and increased mean serum calcium from 9.4±0.2 to 9.8±0.2 mg/dl (P < 0.01). There was a significant positive correlation between the serum la,25(OH)2D and serum calcium in these individuals (r = 0.663, P < 0.01) but not in the normal subjects. The results (a) provide further evidence for abnormal regulation of circulating la,25(OH)2D in sarcoidosis and (b) indicate that the abnormality may exist in patients with normal calcium metabolism. Thus, the defect in vitamin D metabolism in sarcoid apparently is more common than was previously recognized.