In the first part of the study oral glucose tolerance tests (GTT) or insulin tolerance tests (ITT) were performed in 22 lean and 22 obese nondiabetics before and after fasts of at least 6 days' duration. Deterioration of glucose tolerance was greater in lean than in obese individuals. Plasma levels of factors known to influence glucose tolerance (glucagon, growth hormone, free fatty acids, ketones) were significantly higher in fasting lean than in fasting obese subjects. Furthermore, delayed insulin rise (GTT) and decreased insulin sensitivity (ITT) were observed after starvation in lean subjects but not in the obese, which could explain the greater deterioration of glucose tolerance in the lean population. In the second part of the study glucose and fructose tolerance were compared during 4-hour infusions of these substrates (0.5 g/kg/h) in 8 normal subjects before and after two 4-day fasts. After starvation, glucose as well as fructose infusion resulted in plasma levels of the infused hexose significantly higher than in control, and the rise in plasma lactate and pyruvate was delayed. These results contradict the view widely held in the literature, that fructose metabolism remains unimpaired in the fasting state.