The avidin-biotin complex was used for the selective ultrastructural labeling of terminal cell surface galactosyl residues. Rabbit bone marrow cells were treated with the enzyme galactose oxidase in the presence of biotin hydrazide. Subsequent treatment with ferritin-avidin conjugates enabled the electron microscopic visualization of terminal membrane-based galactose and/or N-acetylgalactosamine on these cells. All stages of erythroid development were characterized by high levels of exposed cell surface galactose, whereas all leukoid cells in the same preparations were virtually unlabled by the above method. Modulations in the distribution of these surface determinants during differentiation and maturation of rabbit erythroid cells were found to concur in inverse fashion with respect to that of terminal sialic acids. Neuraminidase treatment, before the above labeling procedure, resulted in the exposure of additional galactosyl residues on the surface of all bone marrow cell types.The results indicate that a galactose-bearing glycoconjugate(s) may comprise an erythroidspecific membrane constituent of rabbit bone marrow cells. The high density of galactose on the surface of even the earliest erythroid precursors may eventually enable the identification and isolation of a stem cell, which already contains the erythroid-specific galactoconjugate(s). The results suggest that variations in the spectrum of cell surface carbohydrates may serve as recognition signals in the complex set of intercellular interactions which occur during the development and maturation of the erythrocyte. The occurrence of similar but species-specific variations in the complement of surface heterosaccharides during erythroid development of humans and other mammals supports this contention.A considerable body of evidence has been accumulated concerning the primary role of cell surface saccharides in the control of cellular behavior and fate of blood cells (1-3). For example, the integrity of surface sialic acids and their continuity with respect to the carrier molecule on the cell surface have been linked to the control of the survival of circulating erythrocytes (4--13) and the phagocytosis of extruded erythroid nuclei in most mammals (14,15). In addition, changes in the normal level and/or distribution of surface sialic acid and terminal galactosyl residues have been implicated in the maturation, the release into circulation, and the homing of lymphoid cells (16,17), as well as the turnover of circulating sialoglycoproteins (18) and the pathological expression in certain diseased blood cells (6,19).It is generally believed that cell surface sialic acids have a "protective" role owing to a masking of cryptic recognition sites, e.g. specific saccharides (20, 21) and antigenic sites (7,22). Since, in most cell membrane glycoconjugates, sialic acid is attached either to a galactose or to an N-acetylgalactosamine residue (23,24), the masking and unmasking of these constituents are believed to be particularly important in the abovemention...