The effects of acute and chronic endotoxin treatment on the plasma levels of insulin and glucagon and their binding to rat liver plasma membranes were examined. Both acute and chronic endotoxin administration increased plasma glucagon levels and decreased the glucagon to insulin molar ratio. Acute, but not chronic, endotoxin decreased blood glucose and insulin levels. Glucagon binding was increased in membranes prepared from the acutely treated rats. However, in membranes obtained from rats treated chronically with endotoxin, only insulin binding was increased. The increases in the binding of both insulin and glucagon were the result of increases in receptor sites.