Epstein-Barr virus (EBV) infection and Plasmodium falciparum malaria are two known cofactors in the aetiology of endemic Burkitt's lymphoma. To assess the relation between these factors, limiting dilution analysis was used to assess the number of EBV-carrying B cells in the circulation of Gambian children during and after acute malaria. Numbers of virus-carrying cells were five times higher in acute malaria patients and in UK patients with infectious mononucleosis than in convalescent malaria patients and in healthy control adults from the UK. Spontaneous outgrowth in limiting dilution cultures from acute malaria samples was inhibited by acyclovir, a viral DNA polymerase inhibitor. The mechanism of outgrowth, therefore, was virus release from the in-vivo infected cell, which led to infection and immortalisation of co-cultured normal B cells. The findings provide evidence that acute malaria is associated with an increase in the number of EBV-carrying B cells in the circulation. Because of this increase, there is a greater chance of a cytogenetic abnormality occurring in such a cell, with consequent evolution of Burkitt's lymphoma.