TheCalophyllumgenus is well-known for its antimicrobial and cytotoxic activities, and therefore, we analyzed these biological activities for resins ofCalophyllum antillanumandCalophyllum inophyllumgrowing in Cuba.C.antillanumresins showed a potent activity againstPlasmodium falciparum(IC50 = 0.3 ± 0.1 μg/mL), while its cytotoxicity against MRC-5 cells was much lower (IC50 = 21.6 ± 1.1 μg/mL). In contrary, the resin ofC.inophyllumshowed an unspecific activity. The presence of apetalic acid, isoapetalic acid, calolongic acid, pinetoric acid I, pinetoric acid II, isocalolongic acid, pinetoric acid III, and isopinetoric acid III inC.antillanumresins was also confirmed. These results demonstrated for the first time the potential activity ofC.antillanumresins againstP.falciparum. Copyright © 2015 John Wiley & Sons, Ltd.