The apical membrane antigen 1 (AMA1), a crucial protein for the invasion of Plasmodium merozoites into red blood cells, is a leading malaria vaccine candidate, but has shown little efficacy in clinical trials so far. Here, the authors show that vaccination with a complex of AMA1 and rhoptry neck protein 2 (RON2) can induce antibody-mediated complete protection against a lethal Plasmodium yoelii challenge in mice. It is likely that the protein complex mimics the functional form of the proteins more closely, thereby inducing more potent protective antibodies.