When virulent group A streptococci of M type 24 were incubated in fresh heparinized whole blood or in blood reconstituted from cellular elements and plasma, little uptake by neutrophils occurred as determined by light microscopy. When fresh human serum (with or without added heparin) was substituted for plasma, uptake occurred promptly. Uptake in serum could be prevented by adding either plasma or purified human fibrinogen to the incubation mixtures, or by pretreating the organisms with plasma or fibrinogen. Fibrinogen solutions absorbed with purified homologous M protein and centrifuged to remove precipitates lost their inhibitory activity. Uptake in serum depended on heat-labile factors. Immunofluorescent staining of bacteria using fluorescein-labeled antibody to the third component of complement showed that streptococci incubated in fresh serum bound complement evenly over the entire cell surface, whereas streptococci incubated in fresh plasma or in serum plus fibrinogen fluoresced only at some of the cross-walls between adjacent daughter cocci and at occasional terminal cocci. In electron micrographs, the surface fibrillar layer of streptococci treated with plasma or fibrinogen lost its hairlike appearance and became a dark band that stained heavily with ferritin-labeled antifibrinogen. We conclude that the known antiopsonic effect of M protein derives in part from binding of fibrinogen.