Conventional insulin therapy does not correct the counter-regulatory abnormalities of insulin-dependent diabetes mellitus. Pancreas transplantation is an alternative therapy that restores the endogenous insulin secretion in diabetes. In this study, the effects of segmental pancreas transplantation on counter-regulation to mild hypoglycaemia were evaluated. Glucose kinetics and the counter-regulatory hormonal responses were assessed in eight insulin-dependent diabetics with end-stage renal failure who had received pancreas and kidney transplantation 1 year previously, seven diabetic uraemic subjects (candidates for combined transplantation), five patients with chronic uveitis on immunosuppressive therapy comparable to pancreas recipients and 10 normal subjects. Insulin (0.3 mU kg-1 min-1) was infused for 2 h to induce mild hypoglycaemia (plasma glucose 3.2-3.5 mmol l-1) and exogenous glucose was infused as required to prevent any glucose decrease below 3.1 mmol l-1. After transplantation, two of eight recipients had hypoglycaemic episodes reported in their medical records. During the study, hepatic glucose production was rapidly suppressed in the controls and in the patients on immunosuppression (-80 +/- 7 and -54 +/- 7%, P < 0.001 vs. basal), and rebounded to the baseline values within 1 h (-3 +/- 1 and -6 +/- 2%, P = NS vs. basal). The transplant recipients had similar suppression in the first hour (-88 +/- 8%, P < 0.001 vs. basal), but the suppression persisted in the second hour (-69 +/- 11%, P < 0.001 vs. basal) indicating a lack of glucose counter-regulatory response.(ABSTRACT TRUNCATED AT 250 WORDS)