Preliminary data from an ongoing epidemiological survey in the pastoral zone of Samorogouan (Ke´ne´dougou) indicate the occurrence of multiple-drug-resistant Trypanosoma congolense. Despite frequent trypanocidal drug treatments with diminazene aceturate (Berenil ®, Hoechst) at 7 mg/kg body weight (bw) at intervals of 2 to 4 weeks, no significant drop in the prevalence of African animal trypanosomosis (AAT) was observed. To examine a suspected drug resistance, 20 Zebu cattle, naturally infected with T. congolense and/or T. vivax, were transferred in December 1989 from Samorogouan into a fly-proof stable. Diminazene aceturate at 7 mg/kg bw cured infections of T. vivax, but was ineffective against T. congolense. Likewise, treatments with homidium bromide (Ethidium ®, FBC) at 1 mg/kg bw and isometamidium chloride (Trypamidium ®, Rhoˆne Me´rieux) at 1 mg/kg bw, respectively, proved to be ineffective. Corresponding chemotherapeutic trials in previously unexposed Zebu bulls and Sahelian goats infected with one primary T. congolense isolate from Samorogouan demonstrated a high level of resistance to diminazene aceturate (7 mg/kg bw in cattle and 17.5 mg/kg bw in goats), isometamidium chloride (1 and 2 mg/kg bw i.v. in goats) and quinapyramine sulphate (Trypacide‘S’ ®, Rhoˆne Me´rieux) at 5 mg/kg bw in goats. The appearance of a multiple-drug-resistant strain of T. congolense emphasizes the urgent need for new chemical substances as trypanocidal drugs and the increasing importance of efficient vector control.