A longitudinal, prospective study to examine the relationship between the outcome of infection with Plasmodium falciparum parasites and in vitro T-cell proliferative responses to a P. falciparum schizont extract (PfSE) was conducted in a village in south-eastern Gabon, an area where malaria is holoendemic and transmission is intense and perennial. The donor's age was found to have a strong independent influence on all malariometric indices. At the community level, the in vitro lymphoproliferative response to PfSE was bimodal with 30% of the villagers studied showing persistently low responses. The frequency of low or high responders within the study population did not show any consistent relationship with the community parasite rates or the number of either patent parasitaemic episodes or clinical malarial attacks per individual. At the individual donor level, the response was negatively correlated with P. falciparum parasite density in those donors who were parasitaemic at the time of sampling. High in vitro lymphoproliferative responses to PfSE were predictive of resistance to clinical malaria. The PfSE-induced in vitro lymphoproliferative response was dependent on antigen presenting cells, CD4+ T-cells and UCHL-1+ cells.