Two highly inbred strains of mice were found to differ in habituation of activity repeatedly assessed in a toggle-box exploration task. The recombinant inbred (RI) strains derived from their cross resembled either one or the other parent strain, suggesting that a single gene exerts a marked influence on this behavior. The influence of an acute ethanol injection on activity in an open field was found to differ among 19 inbred strains. In 6 strains significant decreases in activity from the previous day's scores were seen; in two strains activity increased; and in 11 strains, no significant change was seen. Genetic specificity must, therefore, be considered in the interpretation of pharmacologic substrates for activity in mice. Lines of mice selectively bred for high and low open-field activity are suggested to offer an ideal subject population for neuropharmacologic studies.