A comparison of the metabolic and gastroentero-pancreatic hormonal responses of ten obese and eight lean subjects to 12 h and 36 h fasts has been made. Each subject was given a 50 g oral glucose tolerance test at the end of both 12 h and 36 h starvation. After the 12 h fast blood glucose and 3-hydroxybuty-rate were similar in each group but blood glycerol was 30% higher in the obese subjects. Plasma insulin and vaso-active intestinal polypeptide were also higher in the obese subjects after 12 h starvation. After 36 h starvation in the lean subjects blood glucose was unchanged but on refeeding with 50 g oral glucose, glucose tolerance was impaired. In the same group blood glycerol and 3-hydroxybutyrate rose after 36 h starvation. Plasma glucagon, secretin and vaso-active intestinal polypeptide rose after 36 h starvation in the lean subjects but plasma insulin was unchanged. Refeeding with oral glucose suppressed the increased plasma glucagon, secretin and vaso-active intestinal polypeptide. After the 36 h fast in the obese subjects, blood glucose was unchanged, blood glycerol fell, but blood 3-hydroxybutyrate rose although to a reduced level in comparison with the lean subjects. In the obese group there was no change in plasma glucagon, secretin or vaso-active intestinal polypeptide after 36 h starvation, although plasma insulin fell. The results show different metabolic and gastro-entero-pancreatic hormonal responses to fasting in lean and obese human subjects and suggest an important metabolic role of glucagon, secretin and vaso-active intestinal polypeptide during starvation.