To determine whether increments in circulating GH concentrations within the physiological range would exert insulin-like as well as insulin-antagonistic actions in man and, if so, whether both actions would occur in hepatic and extrahepatic tissues, normal volunteers (n = 6) were infused with human GH (hGH; 100 ng/kg . min) for 6 h along with somatostatin (100 micrograms/h) to suppress insulin, glucagon, and hGH secretion and also with sufficient insulin (100 microU/kg . min) to maintain a constant plasma insulin level. During the final 2 h, glucose (2 mg/kg . min) was infused. In control studies, saline was infused instead of hGH. Infusion of hGH increased plasma hGH to 35 ng/ml. Plasma glucose decreased to 60 +/- 2 mg/dl compared to 67 +/- 1 mg/dl observed in control studies (P less than 0.05); this greater hypoglycemia was due to both greater suppression of hepatic glucose production (P less than 0.05) and greater augmentation of glucose clearance (P less than 0.05). These insulin-like effects of hGH were no longer evident after 2 h. Subsequently, when glucose was infused, plasma glucose increased to 133 +/- 4 mg/dl compared to the 104 +/- 6 mg/dl observed in control studies (P less than 0.01). This greater hyperglycemia was due to both impaired suppression of hepatic glucose production (P less than 0.001) and decreased glucose clearance (P less than 0.01). These results indicate that physiological increments in plasma hGH cause both insulin-like and insulin-antagonistic effects in man and that these actions occur in hepatic as well as extrahepatic tissues. The insulin-like actions of hGH are transient.