Scintigraphic experiments and radioactivity measurements of tissues have shown that the radioactivity of 51Cr-labelled and neuraminidase-treated rabbit erythrocytes is rapidly accumulated in liver and spleen. Sequestration of these erythrocytes by liver and spleen was demonstrated by light and electron microscopy of theses tissues after perfusion of the rabbits with solutions for tissue fixation. In liver the phagocytic activity of Kupffer cells was increased after injection of desialylated erythrocytes, while in spleen a significantly enhanced number of erythrocytes was found attached to the sinusoidal walls and in the reticulum of the red pulp. It was shown by scanning electron microscopy that neuraminidase-treatment did not influence the shape of erythrocytes. Desialylated and 51Cr-labelled erythrocytes from the cow are rapidly cleared from the blood-stream with a half-life time of about 3 h. It was shown in an in-vitro test that they adsorb to surviving slices from liver and spleen derived from the same animal. The amount of radioactivity adsorbed is appreciably enhanced in the presence of homologous serum when compared with buffer only. Human neuraminidase-treated erythrocytes are agglutinated in the direct and especially in the indirect Coombs-tests. The involvement of T-antigen in this phenomenon was largely excluded. The in vitro experiments and antibody consumption tests suggest that immunoglobulins (IgG) and complement from serum may be involved in recognition and sequestration of desialylated erythrocytes by macrophages in vivo.