We studied changes in canine leukocyte glucocorticoid receptors during endotoxin shock. Blood samples for analysis were collected and leukocytes were isolated just prior to and 2 and 6 hours after endotoxin administration. Employing 3H-dexamethasone (3H-Dex) as a ligand, we studied 3H-Dex-specific binding of the leukocytes in dogs and their changes during endotoxin shock. Results from two groups (anesthetized and conscious) showed that the specific binding of the leukocytes decreased significantly 2 hours after endotoxin administration in both groups and 6 hours after endotoxin in anesthetized dogs. In conscious dogs, the specific binding returned to normal by 6 hours. No correlation was found between the changes of serum cortisol and 3H-Dex-specific binding. It may be suggested that perturbations in glucocorticoid hormone action at the receptor level might be involved in the pathogenesis of endotoxin shock.