During behavioral tests of alcohol sensitivity, rapid alcohol-opposing reactions may constitute an important mechanism in reducing the acute performance-impairing actions of alcohol. The alcohol-sensitive ANT (alcohol nontolerant) rats achieve lower plasma corticosterone concentrations after a tilting plane test of alcohol sensitivity (2 g ethanol/kg, IP) than the alcohol-insensitive AT (alcohol tolerant) rats, suggesting a dampening of activated stress mechanisms in the ANT rats. We have extended the comparison of these rat lines by examining central and peripheral stress responses to an acute 10-min swimming stress without ethanol administration. After the stress, plasma and adrenal corticosterone concentrations, adrenal dopammine concentrations, binding of [ 3H]Ro 5-4864 to adrenal membranes, and hypothalamic norepinephrine turnover were lower in the ANT than AT rats. Habituation to daily handling did not affect the stress effects or the differences between the rat lines. These results suggest that the alcohol-sensitive ANT rats have a diminished reaction to general stress, even in the absence of ethanol. This may impair their capacity to overcome the sedative and motor-impairing effects of moderate ethanol doses.