This study characterized the behavioral response to cocaine in two strains of mice, the C57BL/6J and 129/J strains, commonly utilized as host strains for transgenic and "knockout" mice. The psychomotor stimulating effects of four doses of cocaine (2.5, 5.0, 10.0, and 15.0 mg/kg/injection) with a saline control, administered in a "binge" pattern (three equal injections at hourly intervals) for 3 days were examined in adult male C57BL/6J and 129/J mice. Behavioral stereotypy in the home cage, was rated 15, 30, and 45 min following each injection. Spontaneous locomotor activity in the home cage was also monitored. Cocaine, at doses of 10.0 or 15.0 mg/kg, produced behavioral stereotypy in both C57BL/6J mice (p < 0.0001) and 129/J mice (p < 0.0001), whereas lower doses did not. The magnitude of stereotypy was significantly lower in 129/J mice than in C57BL/6J mice receiving identical doses of cocaine. C57BL/6J mice also demonstrated a dose-dependent cocaine-induced stimulation of locomotor activity following administration of 10.0 or 15.0 mg/kg of cocaine (p < 0.0005). In contrast, 129/J mice did not exhibit increased locomotion in response to any dose of cocaine tested. These results demonstrate that strain differences in drug-induced behavior may be more pronounced in one measure (i.e., locomotor activity) than in another (i.e., stereotypy) and indicate the importance of multiple behavioral measures.