The cellular and humoral immune responses to Plasmodium falciparum and P. vivax recombinant circumsporozoite (rCS) proteins were studied in two populations in the Brazilian malaria-endemic region. One group of subjects lived in an urban area that was free from the risk of malaria and was exposed to the disease through short visits to the endemic area. The other group had lived for approximately 10 years in a rural area, where they were continuously exposed to transmission. Proliferative responses to rCS proteins were observed in 50% of 16 adults not continuously exposed to malaria but in only five of 48 subjects (10%) resident in the transmission area. The antibody responses to rCS proteins were approximately 50% in both groups. The interferon-gamma (IFN-gamma) response evaluated only among continuously exposed subjects was low. There was no association between the presence of antibodies and the detection of proliferative or IFN-gamma T cell responses. These findings suggest that continuous exposure to malaria in areas of low endemicity may lead to a specific decrease of the in vitro T cell function.