Ca absorption is regulated by 1,25(OH)2D, and serum values vary inversely with Ca intake. In sarcoidosis, 1,25(OH)2D is produced by alveolar macrophages in response to y-interferon, and patients may develop hypercalcemia after prolonged exposure to sunlight and increased dermal production of vitamin D3. To determine if increased Ca intake suppresses serum 1,25(OH)2D in normocalcemic patients and to identify those at risk, 17 normal subjects and 11 patients were studied on a metabolic ward for two and one-half days while receiving first 400 and then 1,000 mg/d of Ca. On the low Ca intake, serum angiotensin-converting enzyme (ACE), an index of disease activity, was higher in only three of the patients than in the controls, mean serum 1,25(OH)2D was higher in the patients, and mean serum total Ca, serum Ca ", and urinary Ca were not different in the two groups. On the higher Ca intake, mean urinary Ca increased in both groups, but mean serum 1,25(OH)2D was suppressed only in the normal subjects. Thus, 1,25(OH)2D production is abnormally regulated, indicating that (a) normocalcemic patients with sarcoidosis are at risk for developing abnormal Ca metabolism, and (b) a better index of disease activity is provided by the oral Ca suppression test than by serum ACE. (J. Clin. Invest. 1993. 91:1396-1398