ETHNOPHARMACOLOGICAL RELEVANCE: This is the first intercultural report of antimalarial plants in this region. The aim of this study was to document the medicinal plants used against malaria by indigenous people in the Upper Rio Negro region and to review the literature on antimalarial activity and traditional use of the cited species. MATERIALS AND METHODS: Participant observation, semi-structured interviews, and ethnobotanical walks were conducted with 89 informants in five indigenous communities between April 2010 and November 2013 to obtain information on the use of medicinal plants against malaria. We reviewed academic databases for papers published in scientific journals up to January 2014 in order to find works on ethnopharmacology, ethnobotany, and antimalarial activity of the species cited. RESULTS: Forty-six plant species belonging to 24 families are mentioned. Fabaceae (17.4%), Arecaceae (13.0%) and Euphorbiaceae (6.5%) account together for 36.9% of these species. Only seven plant species showed a relatively high consensus. Among the plant parts, barks (34.0%) and roots (28.0%) were the most widely used. Of the 46 species cited, 18 (39.1%) have already been studied for their antimalarial properties according to the literature, and 26 species (56.5%) have no laboratory essays on antimalarial activity. CONCLUSIONS: Local traditional knowledge of the use of antimalarials is still widespread in indigenous communities of the Upper Rio Negro, where 46 plants species used against malaria were recorded. Our studies highlight promising new plants for future studies: Glycidendron amazonicum, Heteropsis tenuispadix, Monopteryx uaucu, Phenakospermum guianensis, Pouteria ucuqui, Sagotia brachysepala and notably Aspidosperma schultesii, Ampelozizyphus amazonicus, Euterpe catinga, E. precatoria, Physalis angulata, Cocos nucifera and Swartzia argentea with high-use consensus. Experimental validation of these remedies may help in developing new drugs for malaria.