The metabolic response to yellow fever immunization was investigated in five obese patients who were consuming a protein-sparing modified fast for 3 wk. Fasting 1/2, 1, and 2 h postprandial values for insulin, glucagon, glucose, lactate, beta hydroxybutyrate, acetoacetate, and free fatty acids were assessed before and the 1st, 3rd, and 5th day after immunization. The hormone and substrate responses to meat ingestion in patients well adapted to a protein-sparing modified fast and prior to infection was a rise in glucagon, no change in insulin, lactate, or ketone bodies and slight increase in serum free fatty acid and glucose levels. Over the entire period a significant (p less than 0.01) postprandial rise in glucagon was noted. Significant increases in insulin (p less than 0.01) and lactate (p less than 0.01) and falls in beta hydroxybutyrate (p less than 0.01) and acetoacetate (p less than 0.01) were noted in the postinfection period. There was also a significant interaction of diet and infection to increase insulin levels (p less than 0.05). The clinically mild infection produced by yellow fever immunization elicits a metabolic response which thus may be useful to investigate intermediary metabolism in the hospital setting.