Mouse alpha 2-macroglobulin (alpha 2M) induced agglutination and lysis of sheep red blood cells depending on temperature and time of incubation in vitro. When these erythrocytes (E) were treated with a subagglutinanting dose of alpha 2M, they were adhered to and phagocytosed by thioglycollate-elicited and BCG-activated mouse peritoneal macrophages. Phagocytosis was not observed when resident peritoneal macrophages were tested. alpha 2M also was able to dissociate sheep red blood cells previously aggregated by IgM anti-E.