Trypanosoma brucei(1) is a unicellular parasite transmitted between African mammals by tsetse flies. T. brucei multiplies freely in the bloodstream of many different mammals, and survives by antigenic variation of the main component of its surface coat, variant surface glycoprotein (VSG)(2,3). Trypanosomes take up transferrin through a heterodimeric transferrin receptor(4-9), the genes for which are expressed in telomeric expression sites along with the VSG gene. There are up to 20 of these expression sites per trypanosome nucleus(3,10-15), but usually only one is active at a time. Different expression sites encode transferrin receptors that are similar but not identical(16). Here we show that these small differences between transferrin receptors can have profound effects on the binding affinity for transferrins from different mammals, and an the ability of trypanosomes to grow in the sera of these mammals. Our results suggest that the ability ro switch between different transferrin-receptor genes allows T. brucei to cope with the large sequence diversity in the transferrins of its hosts(17).