The inhibitory effects of some newly developed H₁-blockers on the step-through active avoidance response in rats were studied in comparison with those of classical H₁-blockers. Single administration of diphenhydramine, pyrilamine, promethazine and chlorpheniramine caused dose-related depressant effects on the active avoidance response. Ketotifen and azelastine caused less potent inhibition than the classical H₁-blockers, while the effects of astemizole and oxatomide were almost negligible in suppressing the response. Following chronic administration of pyrilamine and promethazine, the acquisition of active avoidance response was significantly retarded compared with the control group, where-as new H₁-blockers caused a somewhat but not significantly slower acquisition than the control group. Chronic administration of astemizole and oxatomide caused only transient suppression of the response. However, classical H₁-blockers such as pyrilamine and promethazine caused sustained inhibition for as long as drug administration was continued.