There is a strong clinical relationship between stress and stress-related disorders and the incidence of alcohol abuse and alcoholism, and this relationship appears to be partly genetic in origin. There are marked strain differences in ethanol (EtOH)-related behaviors and reactivity to stress, but little investigation of the interaction between the two. The present study assessed the effects of chronic exposure to swim stress on EtOH-related behavior in three common inbred strains of mice, C57BL/6J, DBA/2J and BALB/cByJ. After establishing baseline (10%) EtOH self-administration in a two-bottle free choice test, mice were exposed to daily swim stress for 14 consecutive days and EtOH consumption was measured as a percent of baseline both during stress and for 10 days afterwards. A separate experiment examined the effects of 14 days of swim stress on sensitivity to the sedative/hypnotic effects of an acute injection of 4g/kg EtOH. Results showed that stress produced a significant decrease in EtOH consumption, relative to pre-stress baseline, in DBA/2J and BALB/cByJ, but not C57BL/6J mice. By contrast, stress increased sensitivity to the sedative/hypnotic effects of EtOH in all three strains. These findings demonstrate that chronic swim stress produces reductions in EtOH self-administration in a strain-dependent manner, and that these effects may be restricted to strains with a pre-existing aversion to EtOH. Present data also demonstrates a dissociation between effects of this stressor on EtOH self-administration and sensitivity to EtOH's sedative/hypnotic effects. In conclusion, strain differences, that are likely in large part genetic in nature, modify the effects of this stressor on EtOH's effects in a behavior-specific manner.