The activities of Mannich base antimalarials, including pyronaridine, have been explored against drug-sensitive (Plasmodium berghei N) and chloroquine-resistant (Plasmodium yoelii NS) rodent malaria parasites in vivo. Lines of these parasites have been developed with resistance to pyronaridine, amodiaquine, or WR 228,258. The responses and patterns of cross-resistance of these lines to Mannich bases and other blood schizontocides are inconsistent. It is concluded that some Mannich bases may prove still to be of value inthe treatment of chloroquine-resistant Plasmodium falciparum infection.