This study was conducted to examine the conditions under which epinephrine (EPI) blocks glucose-induced hyperinsulinemia in normal and endotoxic rats. Nutritional state (fasting vs. feeding) and anesthetic state (conscious vs. sodium pentobarbital anesthesia) were explored as factors that could influence the effects of epinephrine on immunoreactive insulin (IRI) levels. Exogenous epinephrine infusion into control rats significantly blunted hyperinsulinemia in response to an exogenous glucose challenge in fed rats, but not fasted rats. Endotoxin-treated rats (3.3 mg/kg) showed endogenously elevated levels of both EPI and IRI during the hyperglycemic period that is characteristic of early endotoxicosis. All endotoxic rats showed hyperinsulinemia in response to an exogenous glucose challenge, despite the simultaneous presence of elevated catecholamine levels. However, hyperinsulinemia (induced by glucose challenge) was two-fold higher in pentobarbital-anesthetized, endotoxic rats (both fed and fasted) than in respective control rats under the same conditions. These results show that fasted rats are resistant to the insulin-inhibiting effects of epinephrine. In addition, since hyperinsulinemia occurs during endotoxicosis (in both fed and fasted states) despite the presence of elevated catecholamine levels, the results indicate that endotoxin treatment decreases the inhibitory effects of epinephrine on insulin levels. This effect is potentiated by pentobarbital anesthesia and is more pronounced in the fed rat than in the fasted rat.