The objective of this study was to test a hypothesis that the predominant variable antigen type (VAT) repertoire of a single stock of Trypanosoma evansi was limited and small. It was further assumed that six rabbits could produce all antibodies against the predominant VAT repertoire of a stock of T. evansi and the antiserum mixture from the six rabbits containing all the antibodies could completely protect mice against any homologous stock infections and partially protect mice against some heterologous stock infections. Mice were each intraperitoneally infected with 100 parasites of clone-derived and non-clone-derived populations of the YNB stock, Kazakhstan strain or Vietnam strain of T. evansi, and treated with the antiserum mixture when trypanosomes had been detected in the blood. All of the 10 mice infected with either non-clone-derived or clone-derived populations of the YNB stock survived, and some (4/10) of mice infected with the heterologous Kazakhstan strain survived, while all those (10/10) infected with the heterologous Vietnam strain died. These results support the hypothesis that the predominant VAT repertoire of a single stock of T. evansi was limited and small, and have important implications in the consideration of treating human trypanosomosis due to drug resistant strains with antiserum mixture.