We have studied the effects of vitamin D deficiency on pancreatic A- and B-cell function. Four subjects with vitamin D deficiency and 10 healthy subjects were studied. Pancreatic B-cell function was assessed by the insulin response to an oral glucose tolerance test. An insulin tolerance test was used to evaluate pancreatic A-cell function. The patients were then treated with 2000 U/day of vitamin D3 for 6 months, after which the clinical, metabolic, biochemical and radiological features of vitamin D deficiency resolved, and pancreatic A-and B-cell function was repeated. In the vitamin D-deficient subjects pre-treatment and post-treatment serum calcium levels (mean +/- SEM) were 2.22 +/- 0.01 mmol/l and 2.24 +/- 0.01 mmol/l respectively, and 2.27 +/- 0.02 mmol/l in healthy subjects (NS). The pre-treatment level of 1,25-dihydroxy vitamin D (1,25-(OH)2D) of 29.7 +/- 3.3 pg/ml in the vitamin D deficient subjects rose to 70.3 +/- 10.3 pg/ml after treatment (p less than 0.05). The 1,25-(OH)2D level in the healthy subjects was 50.0 +/- 13.7 pg/ml (p less than 0.05 versus pre- and post-treatment values in the patients). Insulin secretion, calculated by the area under the insulin curve, was significantly lower before vitamin D3 treatment in the patients (9.09 +/- 0.7 mU X min, p less than 0.05) compared with the healthy subjects (11.9 +/- 0.5 mU X min) and post-treatment values of the patients with vitamin D deficiency (13.7 +/- 0.5 mU X min). Similar changes were seen in the insulogenic indices (delta I/delta G).(ABSTRACT TRUNCATED AT 250 WORDS)