This chapter focuses primarily on nonimmune ligand–receptor interactions that mediate phagocytosis by mononuclear cells and secondarily on the cellular metabolites produced during the ingestive phase. In the absence of serum, human monocytes ingest unopsonized erythrocytes from rabbits (E r ), from two species of mice (E m ), but not those from sheep (E s ) and guinea pigs (E gp ). The capacity of E r and E m to initiate a monocyte phagocytic response directly parallels their capacity to activate the plasma proteins of the human alternative complement pathway; E s and E gp do not activate this pathway. Monocyte ingestion of E s is greater than that of desialated E s but ingestion of both is reduced in a comparable dose-dependent fashion by the same low concentrations of trypsin that reduce monocyte ingestion of zymosan. The capacity of fibronectin to function as an opsonin was initially described that a plasma protein termed opsonic α 2 -globulin protein or opsonic α 2 -surface binding glycoprotein promoted uptake of gelatin-containing lipid emulsions by rat liver slices. It was later demonstrated that this protein is identical to plasma fibronectin. Both proteins have molecular weights of 440,000, comparable amino acid compositions, and identical antigenic determinants. The opsonic effects of intact plasma fibronectin have generally been studied with four test particles: E s , formalin-treated E S , modified latex beads, and lipid emulsions.