Recent research has demonstrated that an increase in glucose utilization by skeletal muscle occurs in hemorrhagic shock. It is conceivable that the hypoglycemia of gram-negative septic shock is, in part, due to increased glucose utilization by peripheral tissues. The hypothesis tested in this study was that there is an increase in glucose uptake by the isolated innervated and/or denervated forelimb of the dog subjected to endotoxin shock. Results indicate that endotoxin does not affect a net increase of glucose uptake by the isolated forelimb. No increase in uptake occurred when blood glucose concentration was normal. However, when endotoxin hypotension induced a significant hyperglycemia or when arterial glucose concentration was elevated by glucose administration an apparent increase in forelimb glucose uptake occurred. It is concluded that endotoxin does not increase the uptake of glucose by skin and muscle except that it causes hyperglycemia secondary to increased sympathoadrenal discharge in the shock state. Thus, if the dog becomes sufficiently hyperglycemic, an apparent increase in glucose uptake occurs, probably because of accumulation of glucose in the interstititial space of skin and muscle.