In areas of intense malaria transmission, malaria morbidity and mortality is highest in children 3-18 months old. Interventions that reduce malaria exposure early in life reduce morbidity but may also delay development of clinical immunity. We assessed the relationship between intensity of malaria exposure and development of antibody responses. Thirty-nine children were monitored monthly, from birth to > or =2.5 years old (1238 observations), and were divided into 3 exposure categories, on the basis of parasitemic episodes or entomological data. Children with low exposure during the first 2 years of life had higher subsequent levels of antibody to merozoite surface protein-1(19-kDa) (a marker of blood-stage responses) by months 24-35 (P<.05). This inverse relationship decreased as children aged. There was no consistent relationship between exposure early in life and subsequent levels of antibody to circumsporozoite protein (a marker of sporozoite-stage responses). These data suggest that, in areas of intense malaria transmission, during the first 3 years of life, interventions that either reduce the number of asexual parasitemic episodes or lower entomological exposure do not delay the development of antibody responses to blood-stage malarial antigens.