The time sequence and the mechanisms leading to the development of the hypertriglyceridemia of bacteremic sepsis are not fully understood. This study was conducted to determine the mechanisms leading to the early rise in serum triglycerides (TG). Bacteremic sepsis was induced in fasted and parenterally fed rats by intravenous infusion of liveEscherichia colicolonies over a 1 h period every 24 h up to 96 h. Body temperature was elevated from 12 to 48 h afterE. coliinfusion in fasted rats and from 24 to 72 h afterE. coliinfusion in fed rats. The initial rise in serum TG was observed at 3 h afterE. coliinfusion; in fasted rats this elevation was maintained over 72 h. In the parenterally fed rats, hypertriglyceridemia was evident only at the 3 h time point. Serum concentrations of tumor necrosis factor α (TNF-α) were elevated significantly at 60 min after initiating theE. coliinfusion, peaked at 90 min, and declined by 120 min. Immunization with neutralizing goat anti-TNF-α IgG did not block the initial increase in serum TG induced byE. coli.This early rise in TG in fastedE. coli-treated rats was accompanied by a 33% increase in TG secretion in comparison with control rats. TG secretion declined by 27% at 9 h and remained depressed at 12 and 24 h in comparison with time-matched control rats. By 24 h lipid accumulation was evident in the livers of the fasted and fedE. coli-treated rats. Most of the fastedE. coli-treated rats died by 72 h. Parenteral feeding extended survival ofE. coli-treated rats until 120 h. These findings along with the observation that two mechanisms are involved in maintaining the elevation of serum TG duringE. colisepsis suggests that the hypertriglyceridemia may be important in host survival.