A prospective study in 207 children aged 0.5-15 years was carried out to examine the relationship between cellular responses to Plasmodium falciparum ring-infected erythrocyte surface antigen (RESA) and malaria infection and morbidity. The prevalence of lymphoproliferative response to RESA was 13%, IFN-gamma prevalence was 40% and IL-4 prevalence was 22%. Only the IFN-gamma, response to RESA increased significantly with age. When proliferation or stimulation of either cytokine was used to assess T-cell activation the overall frequency of responders increased to 55%. The proliferative and IFN-gamma response to RESA were positively associated. Although there was no association between any of the CMI responses to RESA and concurrent morbidity the prevalence of IL-4 response to RESA was significantly lower in children who experienced clinical malaria in the following year. These results coupled with our earlier data showing a negative relationship between humoral responses to RESA and malaria morbidity support the inclusion of RESA in a subunit vaccine against malaria.