Trypanosoma brucei rhodesiense undergoes antigenic variation in its mammalian host by changing the glycoprotein composing its surface coat. Trypanosome clones which have the same repertoire of variable antigen types (VATs) are said to belong to the same serodeme. Tsetse flies infected with a particular serodeme extrude infective metacyclic trypanosomes which express only a restricted part of this repertoire. As the only known acquired immunity in African trypanosomiasis is VAT-specific this limitation of metacyclic VAT (M-VAT) repertoire could be important in devising a vaccine. This possibility of immunoprophylaxis could depend, however, on whether or not the M-VAT repertoire is conserved over long periods of repeated cyclical transmission and between epidemics. Studies reported here on isolates made from an East African focus of sleeping sickness over a 20-yr period suggest substantial changes in the M-VATs expressed during this time. Furthermore, we have detected change in expression of 3 M-VATs during sequential tsetse transmission of a clone in the laboratory indicating a possible instability in the organization of M-VAT genes.