Intestinal hyperabsorption of calcium (Ca) is frequently observed in sarcoidosis and is characteristic of absorptive hypercalciuria (AH). The potential pathogenetic role of 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] in these two conditions was sought by a careful assessment of the circulating concentration of this vitamin D metabolite and various measures of Ca metabolism before and after prednisolone therapy. In eight patients with sarcoidosis, prednisolone treatment (50 mg/day for 8 days) produced a significant fall in serum 1,25(OH)2D [4.8 +/) 1.9 to 3.3 +/- 1.0 (SD) ng/dl; P less than 0.025], concomitant with a significant decrease in the fracitional intestinal Ca absorption (alpha) from 0.58 +/- to 0.14 to 0.46 +/- 0.13 (+/- SD; P less than 0.005). Urinary Ca and serum parathyroid hormone did not change significantly. However, in six patients with AH, prednisolone therapy resulted in a nonsignificant rise in serum 1,25(OH)2D from 3.6 +/- 0.7 to 4.4 +/- 1.0 ng/dl and no significant fall in alpha (from 0.73 +/- 0.08 to 0.70 +/- 0.10). Urinary Ca was significantly increased in AH patients from 230 +/- 35 to 343 +/- 74 (SD) mg/day (P less than 0.005), while serum parathyroid hormone rose slightly. Serum 1,25(OH)2D and alpha were significantly correlated (r = 0.543; P less than 0.05) for patients with sarcoidosis but not in AH patients. These results suggest that the hyperabsorption of calcium in sarcoidosis is dependent on the serum concentration of 1,25(OH)2D, while in AH it may result from additional vitamin D-independent processes.