Tricyclic antihistaminics have relatively few side-effects compared to other agents that enhance the susceptibility to chloroquine of chloroquine-resistant strains of Plasmodium falciparum. Their efficacy was tested in vitro against resistant and sensitive culture-adapted strains of P. falciparum. Isobologram analysis showed that both cyproheptadine and azatadine exert a marked synergistic action on chloroquine against chloroquine-resistant, but not against chloroquine-sensitive, strains of parasites. Cyproheptadine was about twice as effective as azatadine in reversing chloroquine resistance. Loratadine had no effect on chloroquine against both resistant and sensitive strains of parasites. Our in vitro study showed that cyproheptadine and azatadine may be promising candidates for potentiating chloroquine against resistant malaria parasites.