Fasted, conscious male rats, prepared with arterial and venous cannulas, were given doses (10(10)-10(11) organisms/kg) of live Escherichia coli bacteria. Heart rate and blood pressure were recorded, and arterial plasma samples were taken preinjection and at 30, 180, and 360 min after bacterial administration. Plasma was analyzed for lactate, glucose, norepinephrine (NE), and epinephrine (E). Rats given E. coli were normotensive but with significant tachycardia (P less than 0.05 vs. saline). Plasma NE and E levels increased severalfold during bacteremia (P less than 0.05 for all comparisons). Rats were euglycemic but had a sixfold increase in lactate 6 h (P less than 0.05) after E. coli treatment. Additional rats were subjected to the same protocol but had been made tolerant to bacterial endotoxin by multiple injections over the course of several days. Endotoxin-tolerant rats were also tolerant to live E. coli administration (P less than 0.05, 24 h survival) and had significantly reduced levels of E and NE at 6 h compared with nontolerant bacteremic rats (P less than 0.05). Increases in heart rate and plasma lactate were not significant in endotoxin-tolerant rats. These results suggest profound sympathetic activation during acute bacteremia with attenuated activation in endotoxin-tolerant rats. Tolerance appears to reduce the afferent stimuli that are presumably activated during the course of bacteremia.