In the search for new antimalarial compounds, a subset of a natural product extract library prepared from plant samples collected from Papua New Guinea and Australia was screened for in vitro activity against the chloroquine-sensitive 3D7 and chloroquine-resistant Dd2 strains of Plasmodium falciparum. Using the incorporation of (3H)-hypoxanthine into parasite nucleic acid as a marker of growth, 93 of the 794 extracts screened displayed >40% inhibition against 3D7 infected erythrocytes at 312 姥/mL. Antimalarial activity was confirmed in 48 of these extracts against both 3D7 and Dd2 infected erythrocytes at concentrations between 78 and 390 姥/mL, 14 of which caused >90% growth inhibition of 3D7 at the lowest concentration screened. Extracts were also tested for mammalian cell cytotoxicity to evaluate selectivity of action.