A phagocytic assay performed with human peripheral mononuclear cells and malaria-infected erythrocytes enabled the study of opsonizing antibodies in human serum from donors presenting different levels of protective immunity. Opsonizing activity was found in sera from individuals who could be considered immune, i.e. asymptomatic parasite carriers and subjects residing in endemic regions who presented neither symptoms nor parasites. This contrasted with subjects showing an absence of symptoms or who had experienced only a single malarial infection. All sera contained high levels of antimalarial antibodies, as shown by immunofluorescence assay (IFA). IgG of different subclasses were immunopurified from these sera. All subclasses were shown to bind to the surface of infected erythrocytes by FACS analysis, but only IgG1 and IgG3 were able to mediate opsonization. IgG2 and IgG4 did not opsonize and inhibited the opsonizing activity of IgG1 and IgG3 in competition experiments. These results suggest the existence of a correlation between immune protection, the ability of serum to mediate opsonization of infected erythrocytes and the predominance, in this serum, of IgG1 and IgG3 over IgG2 and IgG4 directed against the surface of the infected erythrocytes.