Fescue toxicosis in cattle occurs as a result of consumption of ergot alkaloids in endophyte-infected (E+, Neotyphodium coenophialum) tall fescue (Festuca arundinacea). The condition is characterized by pyrexia, decreased weight gains, rough hair coats, and decreased calving rates. The objective of this experiment was to investigate whether steers grazing E+ fescue have altered host response to lipopolysaccharide (endotoxin, LPS) challenge compared with steers grazing endophyte-free (E ) fescue. Angus steers (n=8) had continuously grazed either E+ (n=4) or E (n=4) tall fescue grass for 8 months prior to the experiment. The E+ steers had lower body weight, depressed average daily gain, and decreased basal serum prolactin compared with the E steers prior to LPS administration. Each steer received a single bolus i.v. injection of LPS (0·2 µg/kg body weight; Escherichia coli; 026:B6) dissolved in sterile saline, and blood was serially collected every 30 min for 4 h and at 24 h post LPS administration.LPS increased serum tumor necrosis factor-(TNF-), cortisol, and haptoglobin but decreased plasma glucose and IGF-I. Importantly, however, TNF-, cortisol, and IGF-I responses to LPS were greater in E+ compared with E steers. These results indicated that animals grazing E+ fescue had altered integrated metabolic host response compared with animals grazing E fescue. Potentially, combined exposure to E+ fescue and a bacterial LPS could have greater deleterious effects on the animal compared with exposure to only one of the two and would likely lead to increased catabolism.