Laboratory mice infected with a Trypanosoma congolense isolate of water-buffalo origin did not respond when treated with diminazene aceturate (Berenil, Hoechst, West Germany) at 3.5 mg/kg and 7 mg/kg body weight (b.wt.) and also isometamidium chloride (Samorin, May & Baker, Dagenham, England) at doses less than 3 mg/kg b.wt. Effective cure was achieved with isometamidium and diminazene at 3 mg/kg and 14 mg/kg b.wt. respectively; doses in excess of those recommended for use in the field to treat animal trypanosomiasis by the manufacturers. Irregular use of the two drugs on infected water-buffaloes while improperly restrained may be one of the factors responsible for the dual drug resistant T. congolense isolate emerging.