Among populations living in areas endemic for malaria, repeated parasite exposure leads to a gradual increase in protective immunity to the disease. In contrast, this immunity is assumed to disappear after several years of non-exposure. This study was designed to investigate long-term immunity in subjects removed from the risk of exposure. Plasmodium falciparum malaria attacks occurring after short trips to sub-Saharan Africa were compared between 99 European patients and 252 African immigrants who had been resident in Europe for at least four years. Relative to the European patients, those originating from Africa had lower mean +/- SD parasite densities (0.8 +/- 1.5/100 red blood cells versus 1.4 +/- 2.8/100 red blood cells; P = 0.007), less frequent severe disease (4.4% versus 15.2%; P = 0.0005), accelerated parasite clearance and defervescence, and higher levels of antibodies to P. falciparum. These results suggest the persistence of acquired immunity to P. falciparum malaria after several years of non-exposure in African immigrants.