In this paper, in vivo data are presented that suggest a role for host recognition of erythrocyte band 3 in the control of malaria parasitaemia. The course of Plasmodium chabaudi chabaudi AS acute infection in CBA/Ca mice was suppressed or enhanced as a result of treatment on two occasions with enriched preparations of normal erythrocyte band 3 in adjuvant. Co-treatment with band 3 and a recombinant polypeptide encoding the C-terminal region of the P. c. chabaudi AS merozoite surface protein 1, which on its own had no clear effect on parasitaemia, appeared to modulate band 3-induced inhibition. Despite several-fold reductions in ascending parasitaemias in some band 3-immunized groups, there was a lack of obvious or unexpected anaemia prior to, or during infection, indicating a degree of specificity in the parasitaemia modifying response for infected rather than uninfected erythrocytes. These findings support a role for modified host recognition of erythrocyte band 3 in the partial immunity that transcends phenotypic and genotypic antigenic variation by malaria parasites.