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The terpenoid lactone nimbolide, the structure of which has been unambiguously established, was found to inhibit Plasmodium falciparum in culture with a moderate potency. The EC50 against the parasite line K1 from Thailand was approximately 2.0 microM (0.95 microgram/ml). The EC50 of crude aqueous extract of Azadirachta indica var. siamensis (Sadao tree), was 115 micrograms/ml, and of crude ethanol extract was 5.0 micrograms/ml. Since nimbolide is a major constituent in these extracts, it could account substantially for their inhibitory activity. However, neither the crude extracts nor nimbolide showed any activity in vivo against Plasmodium berghei in the mouse either through ingestion (746 mg aqueous extract, 62.5 mg ethanol extract or 12.5 mg nimbolide/kg/day), or subcutaneous injection (93 mg aqueous extract, 31 mg ethanol extract or 12.5 mg nimbolide/kg/day).