It takes a number of years to develop clinical immunity to malaria and malaria pathology is also most evident a number of years after birth. T cells are known to play an important role in defence from malaria parasites but may also contribute to the disease symptoms associated with malaria. T cells which react against malaria parasites have arisen through stimulation with organisms which cross-react with malaria or through exposure to the malaria parasites themselves and express a memory phenotype (CD45Ro+, CD45Ra-, CD4+). T clones which have arisen through exposure to cross-reactive organisms may be expected to home to the tissues where initial exposure occurred as determined by tissue-specific adhesion molecules on the lymphocyte surface. Such tissues may not be appropriate to parasite killing and localization of T cells in such sites may contribute to the immunopathology of malaria. The sharp increase in immunity and decline in pathology observed in later childhood in malaria endemic areas may result from an increase in the number of T cells induced by the parasite itself (as opposed to cross-reactive organisms). Such T cells may not have a preferential trafficking to other organs and may be more likely to circulate through the spleen. Splenic changes may also allow more malaria-specific T cells to concentrate in the spleen and may facilitate interactions between T cells, monocytes, neutrophils and parasites resulting in parasite death. Whereas cytokines secreted by parasite-reactive T cells in all locations may contribute to cerebral malaria and other forms of pathology, cytokines in the spleen at least, should directly contribute to parasite death.