Multinucleated giant cells are commonly found in a wide variety of inflammatory reactions. They are formed at sites of tissue injury by fusion of freshly exuded monocytes, the rate of fusion being dependent on a range of extracellular and intracellular factors. Electron miscroscopy shows that the pooled components of the fused monocytes are not randomly dispersed in the syncytium, but are highly reorganized into a functioning unit. In addition, histochemical and biochemical profiles of cell populations containing these polykarya display a range of metabolic activities, including DNA synthesis, which, on occasions, is followed by successful mitotic division and the formation of polyploid daughter cells. Fusion results in the loss of some surface receptors which in turn interferes with the phagocytic performance of polykarya, which is generally less pronounced than their mononuclear precurses. In addition, polykarya are not as actively motile as macrophages although phenomena of contact inhibition are less obvious. On the other hand, the multinucleate giant cells display prominent exocytosis which may aid in the degradation of extracellular material. The properties of macrophage polykarya contrast with macrophage homokarya produced in vitro. The latter are actively phagocytic, do not synthesize DNA, and have a longer half-life than the syncytia produced in chronic inflammatory reactions. It may well be that the polykarya in such reactions are not true homokarya.