IGHG3 and parasitic infectious disease: Here, we provide major new evidence that antibody-dependent opsonic phagocytosis of merozoites is an important mechanism in acquired human immunity, contributing to the control of parasitemia in vivo. We demonstrate that opsonic phagocytosis of merozoites is mediated by IgG, primarily through cytophilic IgG1 and IgG3 antibodies to merozoite surface antigens, and leads to activation of monocytes with subsequent release of pro-inflammatory cytokines that could further enhance parasite clearance in vivo.