Locomotor activity responses to sub-hypnotic doses of ethanol (ETOH) were assessed in selected lines of mice (LS and SS), inbred strains, and their F1 hybrids. Data were obtained as photocell beam interruptions in a 15-min test for a dose range of 0 to 2.75 or 3.5 g/kg for LS and SS mice, respectively. Biphasic dose-response curves were obtained for LS and SS mice with the SS mice showing a sedative limb of the dose-response curve shifted to the right. The effects of 2.0 g/kg ETOH were also assessed in a diallel cross of the selected LS/SS lines and C57BL/6Abg and MOLD/RkAbg inbred strains. The 2.0 g/kg dose produced a wide range of responses, from sedation in C57BL/6Abg mice to extreme activation in SS and MOLD/RkAbg mice, and no effect in LS mice. The responses of F1 hybrids reflected a typical pattern of partial dominance, with heterosis in some crosses. When present, dominance was in the direction of greater locomotor activation. These patterns were confirmed by biometrical genetic analysis of the 4 × 4 diallel cross of the two lines and the two inbred strains. The data indicate that loci in addition to those responsible for selection for sedative sensitivity in LS and SS mice can influence locomotor activation produced by sub-hypnotic ETOH doses, and that SS and MOLD mice show locomotor activation for different genetic reasons.