ABSTRACT Naturally acquired antibody responses provide partial protection from clinical malaria, and blood-stage parasite vaccines under development aim to prime such responses. To investigate the determinants of antibody response longevity, immunoglobulin G (IgG) antibodies to several blood-stage vaccine candidate antigens in the sera of two cohorts of children of up to 6 years of age during the dry seasons of 2003 and 2004 in The Gambia were examined. The first cohort showed that most antibodies were lost within less than 4 months of the first sampling if a persistent infection was not present, so the study of the second-year cohort involved collecting samples from individuals every 2 weeks over a 3-month period. Antibody responses in the second cohort were also influenced by persistent malaria infection, so analysis focused particularly on children in whom parasites were not detected after the first time point. Antibodies to most antigens declined more slowly in children in the oldest age group (>5 years old) and more rapidly in children in the youngest group (<3 years old). However, antibodies to merozoite surface protein 2 were shorter lived than antibodies to other antigens and were not more persistent in older children. The age-specific and antigen-specific differences were not explained by different IgG subclass response profiles, indicating the probable importance of differential longevities of plasma cell populations rather than antibody molecules. It is likely that young children mostly have short-lived plasma cells and thus experience rapid declines in antibody levels but that older children have longer-lasting antibody responses that depend on long-lived plasma cells.