The domestic fowl is reported to be extremely resistant to E. coli endotoxemia. We reported (Merrill et al., 1978) that in our hands this species displayed a lowlevel sensitivity similar to that seen in mammals. The discrepancy between previous reports and our recent findings could result from 1) seasonal differences in the responses of the domestic fowl to endotoxemia, 2) the age and nutritional status of animals used in these various studies, and/or 3) the toxicity of the different endotoxins used. Since there is a paucity of information regarding seasonal influences on the responses of experimental animals to shock and trauma, we have extended our earlier studies (conducted in October, fall group) to each of the remaining seasons of the year. Overnight, fasted, unanesthetized white Leghorn roosters (N=38) weighing 2.44±0.6 kg were injected intravenously with an E. coli endotoxin suspension (2.5 mg/kg). A separate group of birds (N=8) were injected with 0.9% saline. Plasma glucose, lactate, corticosterone, arterial blood gases and pH and selected hemodynamic variables were monitored for 24h or until death. Only four of eleven endotoxemic fall birds survived 24 h (LD64). All winter birds (N=9) survived the challenge (LDO), while seven of nine spring and summer-challenged animals (N=9 each group) survived for 24 h (LD22 both groups). The preterminal hypoglycemia and progressive lactacidemia seen in similarly-challenged mammals did not occur in any group. Plasma glucose levels in the fall group (least resistant) were significantly lower than in all other groups. The winter group (most resistant) showed the highest glucose levels. Elevation of plasma corticosterone following the endotoxin challenge was greatest in the winter group and least in the fall group. Similar corticosterone increases were seen in the spring and summer groups. We conclude that resistance to endotoxemia in the domestic fowl is influenced by the season of the year and that such seasonal influences are reflected, in part, by circulating levels of glucose and corticosterone. © 1979 Springer-Verlag.