A 235 kD rhoptry protein produced by the malaria parasite, Plasmodium yoelii is the target of antibodies that protect mice against blood-stage challenge with the virulent YM strain. In the protected animals the parasites are confined to reticulocytes and the course of parasitaemia is reminiscent of an avirulent 17X strain infection. The DNA coding for the rhoptry protein has been identified as a multigene family containing at least four members. Sequence analysis of short DNA clones has identified the C-terminus of the protein; a preliminary analysis of longer clones confirms that the genes are polymorphic. The possible implications of these findings for the biology of the parasite are discussed.