Monoclonal IgM rheumatoid factor-like anti-globulins were produced by in vitro stimulation of naive BALB/c spleen cells with lipopolysaccharide, and by hyperimmunization of mice with merozoites of Plasmodium falciparum, followed by fusion of the spleen cells to mouse myelomas. In vitro, these anti-globulins augmented the inhibitory effects of P. falciparum-specific polyclonal mouse sera and monoclonal IgG1 and IgG2b antibodies by binding to Fc fragments of IgG molecules attached to blood-stage parasites. In some instances, the presence of anti-globulins correlated with an increase in the number of schizonts which failed to disperse merozoites. In other cases, parasitaemia remained low in the absence of the schizont inhibition phenomenon, suggesting that anti-globulins contribute to host cell protection not only by agglutinating merozoites, but also by increasing the density of the antibody coat surrounding the parasites, thus interfering with parasite receptor-erythrocyte ligand interactions. The anti-globulins were not inhibitory when added to parasite cultures containing IgG not specific for P. falciparum. These results may help explain the function of IgM anti-globulins found at elevated serum levels in some patients with malaria or other chronic infectious diseases.