Ten normal adults and ten nondiabetic massively obese subjects were studied following 4--7 days on identical diets. Intravenous arginine challenge resulted in similar glucose and glucagon responses and threefold greater integrated insulin responses in the obese when compared to the normal subjects. Following oral glucose, glucagon responses were similar, whereas both basal and integrated insulin values were higher in the obese subjects. Basal and integrated insulin concentrations were greater during intravenous glucose testing in the obese subjects, whereas similar glucagon suppression was observed in both groups. Hourly blood samples obtained during a 24-hr period revealed that the obese glucose profile differed significantly from the normals. Insulin values were two- to four-fold higher in the obese subjects, whereas no significant difference was observed in the glucagon concentrations. The nadir and peak glucagon concentrations for both groups occurred at 8:00 a.m. and 8:00 p.m., respectively, and were positively correlated with plasma amino acid values, and were similar in both groups.