In contrast to the abundance of detailed information on variant-specific surface coat antigens of African trypanosomes, data on possible common or nonvariant antigens within these protozoa are surprisingly limited. In this study, the cellular localization and protective potential of a previously characterized flagellar pocket membrane (FPM) fraction were determined. Immunogold staining of live trypanosome suspensions at 0 to 4 degrees C by using anti-FPM hyperimmune serum raised in rabbits as the primary antibody revealed specific staining of the parasite surface at the emergence of the flagellum from the flagellar pocket. The same specificity of immunogold localization was obtained for each of three distinct variable antigenic types (VATs) of a serodeme of Trypanosoma brucei rhodesiense Wellcome strain. Products of translated mRNA preparations from each of the VATs were precipitated by the FPM antiserum and revealed identical banding patterns when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by autoradiography. Immunization of mice with FPM fraction protected them against infection by two of the VATs; the third VAT was afforded poor protection. This is the first demonstration of the combined cellular localization, nonvariant nature, and protective potential of a membrane fraction from African trypanosomes.