Thrombospondin-related anonymous protein (TRAP) of the malaria parasite Plasmodium falciparum shares two sequence motifs with other proteins which possess adhesive properties. Recently, findings indicate that TRAP is an antigen which contributes to antisporozoite immunity. We have cloned and expressed the TRAP coding sequences in Escherichia coli to investigate the human humoral immune response against this protein in a region of malaria endemicity of West Africa characterized by a seasonal transmission. Our results show that antibodies against TRAP are present in infected individuals. The anti-TRAP antibodies were analyzed in both a longitudinal and a prospective study. The longitudinal analysis shows seasonal fluctuations of the levels of specific antibodies as well as age-dependent quantitative differences. The immune response is long-lived in most of the adults and some of the older children but short-lived in young children. More importantly, the prospective analysis suggests that the presence of anti-TRAP antibodies in older children before the beginning of malaria transmission correlates with the subsequent control of parasite densities.