Twenty-one alkaloids have been assessed for activities against Plasmodium falciparum (multidrug-resistant strain K1) in vitro; 18 of these are reported for the first time. Two protoberberine alkaloids, dehydrodiscretine and berberine, were found to have antiplasmodial IC50 values less than 1 muM, while seven alkaloids-allocrytopine, columbamine, dehydroocoteine, jatrorrhizine, norcorydine, thalifendine, and ushinsunine-had values between 1 and 10 muM. These results are discussed in the context of structure-activity relationships. Compounds were also assessed for antiamoebic and cytotoxic activities, but none was significantly active except for berberine, which was moderately cytotoxic.