Data are presented on the rate of removal of tolbutamide from the blood from studies in heavy drinking, unemployed, male alcoholic subjects. In such subjects tolbutamide was removed faster than it was in normal subjects and faster than in patients with cirrhosis who are not drinking. This rapid removal rate persists for 4 to 9 wk after hospitalization and is reproduced with 400 gm of pure ethanol in 2 or 3 wk but cannot be reproduced with lesser amounts of beverage alcohol taken outside of the experimental study. Similar acceleration of the clearance rates was observed for warfarin and for phenytoin but could not be demonstrated for aminopyrine.