Calcium absorption was measured in eight uremic patients before and after eight days of treatment with 100 or 500 μg of 25 hydroxycholecalciferol (25(OH)D3) per day. Fractional calcium absorption was estimated by administering 47Ca i.v. and orally on separate days and counting forearm radioactivity four hours later. Calcium absorption in four patients with residual renal function rose from 16.3 ± 2.5 to 40.8 ± 5.5% after treatment. In order to determine if the increased calcium absorption was mediated by an increase in the production of 1,25 dihydroxycholecalciferol (1,25 (OH)2D3) by virtue of increased substrate delivery to the 25 hydroxycholecalciferol 1 hydroxylase system present in the residual renal tissue, identical studies were performed in four anephric patients. Calcium absorption in these patients averaged 15.7 ± 2.2% during the control period and rose to 46.0 ± 11.1% after treatment. Increments in serum calcium after treatment were similar in both groups of patients; the mean concentration rose from 9.6 ± 0.3 to 11.0 ± 0.6 mg/100 ml. The results indicate that 25(OH)D3 can improve calcium absorption in the absence of renal tissue suggesting that its conversion to 1,25(OH)2D3 may not be necessary for its effect on the gastrointestinal tract in the uremic patient.