Loxapine, amoxapine and their 8-hydroxylated derivatives were studied by means of [3H]imipramine binding to rat cortical membranes, [3H]spiperone binding to rat striatal membranes, and the inhibition of serotonin uptake by human platelets. As inhibitors of [3H]imipramine binding: amoxapine greater than hydroxyamoxapine greater than loxapine = hydroxyloxapine; as inhibitors of platelet serotonin uptake: hydroxyamoxapine greater than amoxapine greater than hydroxyloxapine greater than loxapine; and as inhibitors of [3H]spiperone binding: loxapine greater than amoxapine greater than hydroxyamoxapine greater than hydroxyloxapine. The antipsychotic properties of loxapine and amoxapine were supported by the binding results, which also indicated the probable antipsychotic activities of the metabolites. All 4 compounds may possess dual action of antidepressant effect as well as antipsychotic effect.