Antimalarial activities have been identified in four microbial metabolites through a screening programme of existing compounds in the Kitasato Institute chemical library. Hedamycin showed selective and potent activity against both drug-resistant and drug-sensitive strains of Plasmodium falciparum. Simaomicin alpha exhibited remarkably strong antimalarial activity, although its activity against a drug-resistant strain was weaker than that against a drug-sensitive strain. The antimalarial effects of triacsins C and D are also reported.