We have attempted to correlate the functional activity of protein 3 with its activity as a receptor for concanavalin A. The concanavalin A agglutination of human erythrocytes is enhanced by adenosine. It varies with time of storage of the blood and is dependent on the concentration of adenosine in the medium. Adenine and/or inosine, which increase cellular ATP, do not substitute for adenosine in enhancing agglutination, and adenosine enhances agglutination of fresh erythrocytes with normal levels of ATP. Thus, it appears that cellular ATP levels are not directly involved in modulation of concanavalin A agglutination by adenosine. Trypsin, which hydrolyzes most of the exposed proteins of the cell surface but does not alter protein 3, enhances concanavalin A agglutination without altering the relative response to the cell to adenosine. Glucose, as well as the glucose transport inhibitors maltose and cellobiose, inhibits agglutination. High concentrations of adenosine reverse the inhibition by glucose and enhance agglutination in the presence of maltose and cellobiose. Treatment of erythrocytes with 4,4'-diisothiocyanostilbene-2,2-disulfonic acid disodium salt, which selectively inhibits the anion transport function of protein 3, substantially inhibits adenosine-supported concanavalin A agglutination. Treatment of erythrocytes with iodoacetate under conditions in which it selectively reacts with glyceraldehyde-3-phosphate dehydrogenase inhibits agglutination. Adenosine protects this dehydrogenase in erythrocytes from inactivation by iodoacetate, over the same concentration range in which it enhances agglutination.