The purpose of the present study was to elucidate the role of catecholamines in mediating the endotoxin-induced increase in glucose uptake of individual tissues. In vivo glucose utilization by selected tissues, assessed by the 2-deoxyglucose (2dGlc) tracer technique, was determined 3 hr following the i.v. injection of Escherichia coli lipopolysaccharide (LPS; 100 micrograms/100 g bw) or saline. Catecholamine action was inhibited by the combined administration of alpha and beta receptor antagonists, phentolamine and propranolol. Adrenergic antagonists alone did not change plasma glucose levels or the glucose metabolic rate (Rg) of the investigated tissues; however, adrenergic blockage resulted in mild hypoglycemia in endotoxemic animals. LPS administration increased in vivo Rg by the liver (571%), lung (229%), spleen (210%), intestine (76%), skin (82%), fat (181%), gastrocnemius muscle (70%), and kidney (61%). There was a significant elevation in the glucose metabolic clearance rate (MCR) by these tissues as well. LPS did not increase Rg by brain and testis. Adrenergic blockade completely prevented the LPS-induced Rg increase in the liver and partially inhibited the elevation in other tissues. The LPS-induced increase in the MCR in spleen, lung, intestine, skin, fat, muscle, and kidney was not altered by adrenergic blockade, indicating that the attenuated Rg in these tissues was the consequence of the decreased plasma glucose concentration observed under this condition. However, in the liver, adrenergic antagonists markedly inhibited the LPS-induced increase in both Rg and MCR. Thus our data indicate that the glucose metabolic response to LPS is partially mediated by catecholamines through the accompanying changes in plasma glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS)