Insulin was withdrawn from 7 patients with Type I (insulin-dependent) diabetes and 4 patients with insulin-dependent diabetes secondary to chronic pancreatitis, both groups without residual beta-cell function. Median plasma glucagon concentrations rose slightly, but significantly after withdrawal of insulin in Type I diabetic patients (from 14 (range: 11-16) to 19 (14-25) pmol/l by 6 h), but not in the patients with secondary diabetes. This was accompanied by a significantly higher increase in blood glucose concentration from 5.1 (4.9-5.7) to 15.2 (12.9-18.1) mmol/l by 6 h in Type I diabetic patients compared with patients with secondary diabetes (from 4.9 (4.3-6.7) to 13.1 (10.9-13.5) mmol/l) (p less than 0.01). Beta-hydroxybutyrate increased to a similar extent in the two groups, whereas no significant increases were found in glycerol and lactate in any of the groups. Increased secretion of glucagon is not essential for the development of hyperglycemia and ketonemia in patients with diabetes secondary to chronic pancreatitis, but may augment the degree of hyperglycemia in Type I diabetic patients compared with patients having secondary diabetes.