The hexane extract from leaves of Vernonia brasiliana (L.) Druce (Compositae) was active in vitro against Plasmodium falciparum and in vivo in mice infected with Plasmodium berghei. This extract was subjected to a bioassay-guided fractionation protocol based on the in vitro model. Lupeol was identified as a compound responsible for the activity, inhibiting the P. falciparum growth by 45% when tested at 25 µg/ml. However, this triterpene was inactive in vivo when 15 mg/kg were administered per os during four consecutive days to mice infected with P. berghei. β-Amyrin and germanicol, isolated from the same fraction that yielded lupeol, were inactive in the in vitro assay.