We studied the relationship between the pancreatic glucoregulatory hormones, insulin and glucagon, and glucose intolerance through the response to food and intravenous glucose in 11 patients with verified hepatic cirrhosis. Blood samples were obtained from the portal vein and the superior vena cava. The results of the systemic vein hormone determinations were compared to results obtained from peripheral vein determination in 10 age-, sex- and weight-matched controls admitted to hospital for minor surgery and to results from ambulant, normal subjects. In the cirrhotics collateral shunting was elevated by transhepatic portography. The cirrhotics and the matched controls had similar glucagon levels and responses, but showed hyperresponsiveness to a meal compared to ambulant normal subjects. Compared to the matched controls the cirrhotics showed glucose tolerance and hyperinsulinism, but compared to normal subjects the hospitalized controls were also glucose intolerant and demonstrated hyperinsulinism. In the cirrhotics, the portal vein/vena cava ratio for insulin was negatively correlated to the degree of collateral shunting. No relationship was found between the degree of portosystemic shunting and fasting concentrations of glucagon and insulin, and the insulin response to glucose. The glucagon response to the meal, was correlated to severity of cirrhosis. The rate constant for glucose disappearance (K-value) was not related to the insulin response, to severity of disease or to degree of shunting. It was, however, correlated to the suppressibility of glucagon secretion as measured in the portal vein. Our results indicate that the glucoregulatory disturbances in compensated cirrhosis are partly caused by non-specific factors which are independent of cirrhosis; the portal-vein hormone responses, however, support the contention that glucagon secretion influences glucose tolerance in cirrhotics.