Inhibitory antibodies specific for the 19-kDa fragment of merozoite surface protein 1 (MSP1(19)) are a significant component of inhibitory responses in individuals immune to malaria. Nevertheless, conflicting results have been obtained in determining whether this antibody specificity correlates with protection in residents of areas where malaria is endemic. In this study, we examined sera collected from a population of semi-immune individuals living in an area of Vietnam with meso-endemicity during a 6-month period. We used two Plasmodium falciparum parasite lines that express either endogenous MSP1(19) or the homologous region from Plasmodium yoelii to measure the MSP1(19)-specific inhibitory activity. We showed that (i) the level of MSP1(19)-specific inhibitory antibodies was not associated with a delay in P. falciparum infection, (ii) MSP1(19)-specific inhibitory antibodies declined significantly during the convalescent period after infection, and (iii) there was no significant correlation between the MSP1(19)-specific inhibitory antibodies and the total antibodies measured by enzyme-linked immunosorbent assay. These results have implications for understanding naturally acquired immunity to malaria and for the development and evaluation of MSP1(19)-based vaccines.