Isolated rat liver macrophages adherent to culture dishes phagocytize selectively senescent rat erythrocytes as well as in vitro aged rat erythrocytes but not young or freshly isolated erythrocytes. Since in vitro aged erythrocytes lack cell bound antibodies and phagocytosis occurs in serum free medium, antibodies do not appear to play a role. Phagocytosis as well as binding of old erythrocytes to liver macrophages is inhibited by N-acetyl-D-galactosamine and related monosaccharides (1-25 mM range) and by corresponding synthetic glycoproteins (10(-6)-10(-10) M range) but not by D-mannose or N-acetyl-D-glucosamine. We conclude that recognition and phagocytosis of senescent and in vitro aged erythrocytes is mediated by the galactose particle receptor on rat liver macrophages.