Desialylated serum glycoproteins have drastically reduced survival times in the circulation compared to native forms of the same proteins. A specific receptor on hepatocytes mediates their clearance by recognition of galactose residues made terminal by removal of sialic acid. This phenomenon was first demonstrated using desialylated ceruloplasmin (7). The newly exposed galactose moieties were implicated as recognition determinants by the findings that treatment of asialoceruloplasmin with galactose oxidase or, a-galactosidase (7) or enzymatic replacement of the missing sialic acid residues (8) markedly prolonged survival in circulation. Subsequently, the generality of the original observation has been established by extension to alternate serum glycoproteins (7) and by the growing list of known glyco proteins susceptible to enhanced clearance due to desialylation (fable 1). Upon the foundation of these initial studies [summarized in an earlier review, see (9)], our current understanding of this process has been built and continues to grow. Two broad and overlapping categories define the studies that have contributed to this understanding. In some, the nature of the receptor molecule and its interaction with ligands have been examined. In others, the relationship between the receptor molecule and the cell in which it resides has been probed. Here, we discuss the results of both of these approaches.