To evaluate the role of calcitriol on insulin secretion in uraemia, nine patients on maintenance haemodialysis, never treated with vitamin D nor with calcium-channel blockers, were studied. Baseline glucose, insulin, C peptide, calcium, intact PTH, and calcitriol serum values were measured, and after an oral load of 75 g glucose, insulin and C peptide were also determined at 15, 30, 45, 60, and 120 min. Following 14 days of treatment with oral calcitriol (0.5 microgram/day), the same study protocol was applied. Serum calcitriol values, which were low as expected, increased after therapy, but did not reach the values observed in healthy controls. Despite no change in total serum calcium, intact PTH values decreased significantly (182 vs 88.3 ng/ml, P less than 0.003). Baseline serum insulin was significantly increased after calcitriol (7.5 vs 35 microU/ml, P less than 0.001). Similarly, an enhancement in insulin secretion following calcitriol was observed at 15 min (34 vs 70, P less than 0.01) and 30 min (57 vs 96 microU/ml, P less than 0.01). Computation of the total area under the curve confirmed these results. Changes in C peptide profile paralleled those described for insulin. These data confirm that vitamin D modulates pancreatic beta-cell secretion and suggest that calcitriol may regulate insulin release in uraemic patients.