We studied the effects of heat-inactivated immune monkey serum on the growth of a partially synchronized culture of Plasmodium falciparum. By light microscopy, parasites within erythrocytes were morphologically indistinguishable from those cultured in normal serum. Immune serum reduced by 90% the number of erythrocytes containing newly invaded rings. Clusters of extracellular merozoites, usually around clumps of malarial pigment, were seen frequently in cultures grown with immune serum but rarely in cultures with normal serum. Electron microscopy confirmed the normal development of intraerythrocytic parasites. In immune serum cultures, electron-dense precipitates were found on the surface of schizonts, merozoites, and the excrescences on the plasma membrane of schizont-infected erythrocytes. Merozoites in immune serum cultures appeared to aggregate by adherence between adjacent surface coats. These findings support the hypothesis that immune serum agglutinates merozoites and thereby inhibits their invasion into uninfected erythrocytes.