The biology of antigenic variation is discussed, and the problems that must be solved to provide a full understanding of antigenic variation are considered. These are (i) the induction of v.s.g. synthesis in the salivary glands of the tsetse fly; (ii) the nature of the restriction on v.s.g. genes that allows only some of them to be expressed in the salivary glands; (iii) the nature of 'predominance' in v.s.g. expression in the mammalian host, and the mechanism by which it operates; (iv) the repression of v.s.g. synthesis in the insect midgut; (v) the anamnestic response that produces expression of the ingested variant in the first patent parasitaemia in the mammalian host; (vi) the mechanism by which only one v.s.g. gene at a time is expressed; (vii) the relationship if any of v.s.g. structure to v.s.g.-associated differences in growth rate and host range; (viii) the role of v.s.g. release within the life cycle and to pathogenesis.