The influence of endotoxic administration (0.5 mg/kg) on hepatic pyruvate kinase activity in normal (nondiabetic) and diabetic dogs was investigated. Pyruvate kinase activity was not affected four hours after endotoxin injection in nondiabetic dogs. However, it was stimulated by 288% in dogs that were made diabetic prior to the administration of endotoxin. Since pyruvate kinase activity in diabetic dogs without endotoxin treatment was not affected, these findings suggest that the stimulatory effect of endotoxin on pyruvate kinase activity in diabetic dogs may be associated with insulin deficiency and/or high ambient blood glucose level.