Twenty-five Shigella strains were tested for their susceptibility to phagocytosis and killing by polymorphonuclear neutrophils (PMN). The studies identified several serum factors that could participate in opsonization. The strains varied remarkably in their susceptibility to killing when heat-stable opsonins were employed, but all strains were killed when exposed to heat-labile opsonins and PMN. The heat-stable opsonin was shown to be IgG, whereas IgM was ineffective in the absence of complement, and 11S IgA was never effective. Heat labile opsonization required immunoglobulin as well as complement, but IgM was the only immunoglobulin demonstrated to participate in this reaction. The alternative C3 activating pathway is required for efficient heat-labile opsonization of Shigella, but some opsonization also appeared to occur through the C1-C4-C2 pathway of C3 activation.