Previously adrenalectomized (ADX) rats were bled to a mean arterial pressure of 40 mm Hg and maintained for 1½ hours. Basal glucose uptake by isolated soleus muscle from ADX normal rats and ADX rats subjected to shock ("shock" muscles) increased with the increase in medium glucose concentration and uptake was similar in both groups of muscles. This indicates that shock per se did not produce any alterations in the basal glucose carrier mechanism. Insulin (0.1 unit/ml) increased uptake in ADX control but not in ADX shock muscles. Maximal stimulation of glucose uptake in shock muscles was observed at an insulin concentration of 0.2 unit/ml insulin. These experiments provide the first direct evidence that the responsiveness of tissues to insulin is altered during shock. This alteration could not be due to increased steroid or epinephrine output during shock.