The in vitro antitrypanosomal activity of methylene chloride, methanol and aqueous extracts of the leaves and twigs of five plant species traditionally used in Benin for the treatment of sleeping sickness were evaluated on Trypanosoma brucei brucei and their selectivity was analysed on Leishmania mexicana mexicana and J774 macrophage-like murine cells. The results showed that the four most active extracts had MIC values ≤19 g/ml (Hymenocardia acida twig and leaf, Strychnos spinosa leaf, Trichilia emetica leaf methylene chloride extracts).All these extracts had a lower activity on L. m. mexicana and J774 cells. Determination of the IC 50 values of the methylene chloride leaf extracts on two strains of trypanosomes (T. b. brucei and T. b. rhodesiense) and two mammalian cell lines (L6 and J774 cells) showed that all extracts possessed some antitrypanosomal activity with IC 50 's ranging from 1.5 to 39 g/ml. All were also toxic to the mammalian cells, but usually with higher IC 50 's. The only exception was the S. spinosa methylene chloride leaf extract which had no toxicity on J774 cells. Although tannins have been identified in most of the species studied, they could not be detected in the most active extracts, just as alkaloids. The presence of flavonoids and quinones may at least in part explain the observed activities of some of the active extracts.