In the search for biologically active plant species, many studies have shown that an ethnopharmacological approach is more effective than a random collection. In order to determine whether this is true in the case of plant species used for the treatment of malaria in Orissa, India, the antiplasmodial activities of extracts prepared from 25 traditionally used species were compared with those of 25 species collected randomly. As expected, plant species used traditionally for the treatment of malaria were more likely to exhibit antiplasmodial activity (21 species (84%) active againstPlasmodium falciparumstrain 3D7) than plant species collected randomly (9 species (32%)). However, of the nine active randomly collected species, eight had not previously been reported to possess antiplasmodial activity while one inactive species had been reported to be active in another study. Of the 21 active species of traditional antimalarial treatments, only six had been reported previously. This study suggests that while the selection of traditional medicinal plants is more predictive of antiplasmodial study, random collections may still be of value for the identification of new antiplasmodial species. Copyright © 2012 John Wiley & Sons, Ltd.