We review here antigenic variation in African trypanosomes with emphas
is on genetic mechanisms and on the expression sites in which the gene
s for Variant Surface Glycoproteins (VSGs) are expressed. There are mu
ltiple expression sites in a trypanosome, but only one of these is act
ive at a time. We discuss recent experiments that provide new informat
ion on expression site regulation, i.e., how inactive sites are kept i
nactive and how the trypanosome switches from expression of one site t
o expression of another one. Trypanosomes can also change the gene exp
ressed by replacing the gene in an active expression site by another V
SG gene. This replacement involves the duplicative transposition of a
silent VSG gene into the expression site, We present a model for the m
echanism of this transposition that incorporates new features and that
explains several unusual characteristics of the transposition process
. We also discuss how new knowledge of nutrient uptake, notably uptake
of host transferrin by trypanosomes, might be used for vaccine develo
pment.