Fourteen non-insulin-dependent diabetic subjects were placed on a balanced diet for 2-3 weeks followed by the same balanced diet alone (group I: control, n = 7) or daily administration of 1 alpha (OH)-vitamin D3 (1 alpha (OH)D3) (group II: 2 micrograms/day, n = 7) additionally for the next 3 weeks. A 75 g oral glucose loading test was conducted before and after the experiment and the plasma insulin response was compared along with the metabolic parameters including serum calcium, phosphorus and serum lipids. The following results were obtained. (1) Total insulin secretion in response to 75 g glucose loading was significantly increased in group II (16.3 +/- 3.9 microU/2 h/ml versus 22.7 +/- 4.9 microU/2 h/ml; P less than 0.05), though no difference was demonstrated in group I. (2) Mean serum calcium level was significantly increased from 9.4 +/- 0.1 mg/dl to 9.6 +/- 0.1 mg/dl (P less than 0.05) and serum free fatty acid level was decreased from 0.80 +/- 0.07 mEq/l to 0.53 +/- 0.07 mEq/l (P less than 0.05) in group II, but not in group I. (3) However, there was no direct correlation between total insulin secretion during a 75 g oral glucose loading test and serum calcium or free fatty acid level. The findings that 1 alpha (OH)D3 enhances insulin secretion and reduces the levels of serum free fatty acid in non-insulin-dependent diabetics provide us with the possibility that vitamin D may play some role in the regulation of insulin secretion.