Resistance developed by the immune system in response to blood-stage malaria is complex in nature, involving humoral and non-antibody effector mechanisms. Different species of malarial parasites may vary in their ability to elicit, or their susceptibility to, those immune effectors. This complexity is enhanced by the different results obtained in vaccinated as opposed to drug-controlled infections. It is therefore important that some attempt be made to unravel these interactions. This is particularly so when we have to decide on methods for assessing the potentiality of antigens to induce protective immunity. In this review the limitations of some in vitro assays of immunity, as well as those of various host-parasite models, are discussed. The relative importance of cell-mediated and humoral immunity in laboratory models and natural infections is also considered in the context of vaccine development.