The biochemical processes that determine the lifespan of mammalian erythrocytes are unknown; one prominent theory suggests that antibody binding to the senescent red blood cell identifies it for removal from the circulation. To address this question, we have used a newly developed procedure for the isolation of aged erythrocytes that involves the biotinylation of rabbit red blood cells, in vivo aging of these cells, and the eventual in vitro recovery of the aged red blood cells by their affinity for an avidin support. Erythrocytes isolated with this method were found to have near-normal levels of cell- associated Ig throughout their 60-day lifespan. These data suggest that IgG accumulation is not part of the normal senescence process for erythrocytes in rabbits.