Monoclonal antibodies have been made against clones of Trypanosoma brucei rhodesiense from the WRATAR 1 serodeme and analyzed by indirect immunofluorescence assay for specificity against homologous and heterologous clones. These antibodies were shown to be variable antigen type (VAT)-specific as they identified the majority of parasites in the homologous clones but few parasites in other clones. The reactivities of these VAT-specific monoclonal antibodies with uncloned human trypanosome isolates from Kenya were compared with the reactivities of polyvalent, VAT-specific rabbit sera on the same isolates. Different reaction patterns were obtained with the two sets of reagents and concordant reactions were less than 20%. Our data indicate that single monoclonal antibodies are not interchangeable for sera in the typing of antigenic variants of African trypanosomes, and multiple monoclonal antibodies for each antigenic variant will probably be needed.