To compare the behavioral effects of psychoactive drugs between two strains of mice. The Kunming (KM) and ICR mice were injected intraperitoneally with caffeine (3, 10, 30, 100 mg/kg), ephedrine (3, 10, 30, 100 mg/kg), diazepam (1, 3,1 0 mg/kg) and chloral hydrate (10, 30, 100 mg/kg), respectively. Ten min after injection, the locomotor activity in the open field was recorded for 2 h. The total distance, the distance ratio to total distance and the time in central region were analyzed for each drugs. Thirty min after injection, the latent time in the passive avoidance test was measured in a shuttle box. Caffeine and diazepam prolonged the latent time, and ephedrine and chloral hydrate decreased the latent time, but there were no differences between the two strains. The two strains of mice exhibited significant differences in the total distance after injection of ephedrine 10 mg/kg, diazepam 3 mg/kg and chloral hydrate 100 mg/kg. Compared to KM mice, ICR mice exhibited an increase in the distance ratio and the time in central region after injection of ephedrine 10-100 mg/kg, but a decrease after diazepam 3-10 mg/kg. KM and ICR mice show no differences in latent time, but significant differences in the total distance, the distance ratio and the time in central region in the locomotor activity. Therefore, selection of mouse strains is important in the study of psychoactive drugs.