The effect of chronic alcohol intake on anesthetic responses to alcohol, thiopental, or diazepam was examined in adult male Sprague-Dawley rats. Alcohol-fed animals were maintained solely on a complete balanced liquid diet containing 6.54% ethanol (w/w) for 21 days; pair-fed control animals received equal amounts of the same diet with alcohol isocalorically replaced by sucrose or dextrin. Nine hours after diets were withdrawn on the twenty-second day, the following drug/dose combinations were administered intraperitoneally to separate groups of alcohol-fed and control rats (10–15 animals in each group): ethanol 2.4, 3.2, and 4.0 g/kg; thiopental 20, 40, and 80 mg/kg; and diazepam 10, 20, and 40 mg/kg. Three different responses were assessed in every animal: 1) loss of righting reflex (induction of anesthesia); 2) response to a painful stimulus (analgesia); and 3) sleeping time (duration of anesthesia). Alcoholfed rats compared with controls were significantly less tolerant of pain at an acute alcohol dose of 2.4 g/kg, and loss of righting reflex and sleeping time were reduced at 4.0 g/kg. All three anesthetic responses were also attenuated in alcohol-fed rats at a diazepam dose of 20 mg/kg. In contrast, none of the three responses was reduced in alcohol-fed rats at any of the three thiopental doses. Thus, chronic alcohol intake sufficient to produce tolerance to anesthetic doses of alcohol in rats also produced cross-tolerance to diazepam but not to thiopental in equianesthetic doses. These results suggest that blanket recommendations for adjusting intravenous anesthetic dosages in alcoholic humans may be inadequate as guides to anesthetic management.