The interferons are a biologically related but physically heterogeneous class of antiviral proteins which are produced by animal cells in response to viral infection or other inducing agents (1).The primary factors which appear to determine the physical properties and molecular weight of each interferon are the animal species of the producing cell (2) and the nature of the inducing agent (3, 4). Moreover, there is also suggestive evidence that different tissues of the same animal may produce different interferons in response to the same stimulus (5). Of particular interest from the standpoint of pathogenesis of viral infection is the role of phagocytic cells in interferon production (6).Among the many questions raised by these observations is whether there are different mechanisms or different genes that control biosynthesis of different interferons. Previous studies have clearly demonstrated that virus-induced formation of interferons by cultures of chick (7, 8) and mouse (8) fibroblasts or cancer cells (9) requires intact capacity to synthesize cellular RNA and protein. However, inhibitors of protein synthesis were not found to prevent interferon formation induced in mice by intravenous injection of bacterial endotoxin (10) or the Pe,icilbium mold product, statolon (11). The failure heretofore to demonstrate endotoxin-induced formation of interferon in cell cultures has precluded a more exacting comparison of interferon induction by viruses and bacterial endotoxin.The present studies were undertaken to define more precisely the mechanisms of synthesis and the nature of interferons produced by parenchymal and phagocytic cells. Explanted rabbit cells and intact rabbits were chosen as experimental models because of their capacity to synthesize large amounts of interferon at an extremely rapid rate in response to viral and nonviral stimuli. The first paper describes the kinetics and cellular mechanisms of interferon synthesis under various conditions. The following report (12) compares some physical properties and molecular weights of the several interferons.