An impressive hypersecretion of growth hormone (GH) occurs in response to an intravenous (iv) glucose load during the febrile phase of a viral infection (sandfly fever) in man. To study the mechanism of such hypersecretion using an appropriate animal model, conscious male rhesus monkeys were given iv glucose tolerance tests (GTT) (0.5 g/kg) on a control day (GTT-1) and at the height of illness (GTT-2) 24 hr after iv inoculation with 108 virulent Diplococcus pneumoniae (n = 9) or 109 virulent Salmonella typhimurium (n = 5). Sequential plasma samples were obtained from femoral vein catheters for radioimmunoassayable GH, glucose, and free fatty acids (FFA). There was no glucose intolerance or FFA abnormalities during GTT-2 in either group. An exaggerated increase in plasma GH occurred during GTT-2 during pneumococcal sepsis with a peak GH of 20.8 ± 5.9 ng/ml at 30 min as compared by paired t test with the control (GTT-1) of 7.8 ± 2.8 at 30 min (p < 0.05). This hypersecretion of GH during GTT-2 also occurred in 2 of 5 monkeys inoculated with S. typhimurium but rarely in control monkeys inoculated with heat-killed D. pneumoniae, a saline placebo, or in those infused iv with normal saline containing no glucose. Chlorpromazine administration for 1 week suppressed the GH hypersecretion during GTT-2 in 7 of 8 additional monkeys with acute pneumococcal sepsis. Alpha adrenergic blockade with phentolamine did not abolish GH hypersecretion during GTT-2. These studies demonstrate in monkeys an exaggerated GH response following an iv glucose load during the stress of acute infection, and suggest that the exaggerated response may be suppressed with chlorpromazine.