We previously reported that antibodies to the central repeat (DDEHVEEPTVA) of Pf155/RESA, a major Plasmodium falciparum antigen, were negatively related to antimalarial protection. We measured levels of isotype antibodies to this epitope and to P. falciparum in 76 Madagascan subjects. Immunoglobulin G (IgG) and isotype antibodies specific for P. falciparum had similar levels in individuals who were considered protected and those who were not (as determined during a longitudinal follow-up). The levels of IgG1 antibodies to (DDEHVEEPTVA)3 were higher in nonprotected subjects. The levels of total IgG and of other isotype antibodies had a similar tendency to be higher in nonprotected than in protected individuals.