The study of inherited RBC resistance to malaria has increased our knowledge of the biochemistry and physiology of the host-parasite interaction and suggested potential sites for therapeutic intervention. Discovery by Jensen and Trager of the in vitro culture system for P falciparum has facilitated research in this area. Known RBC defects may affect invasion, growth, or merozoite liberation (Fig 1). Significant advances made in understanding mechanisms underlying protection against malaria should not obscure the fact that the data are far from complete. More knowledge is needed about the influence of the erythrocyte cytoskeleton on invasion and growth of parasites as well as the potential role of phospholipids, erythrocyte enzymes other than G6PD, or other metabolic products. Application of DNA analysis and recombinant technology may have an increasing impact on study of the interaction of RBC defects with malarial parasites.