Since the review on interferons that appeared in the Annual Review of Biochemistry in 1982 (1), many developments have occurred. These have resulted in a vast expansion of the literature concomitant with the availability of relatively large quantities of purified interferons from natural sources as well as recombinant DNA technology_ New insights have been gained in their biochemistry, molecular biology, and clinical application. Because this reн view is limited in size, it represents a highly selective presentation of the highlights of the past five years. Studies on the numerous biological effects of interferon have only been mentioned in brief. As a whole, this review should provide a scaffold upon which the reader can build. The authors thank our numerous colleagues who were extremely gracious in providing reprints and preprints so that this review could be as up to date as possible. There appear to be three major classes of interferons (2, 3): leukocyte or alpha'interferon (IFN-a); fibroblast or beta interferon (IFN-f3); and immune or gamma interferon (IFN-y). These three classes seem to be present in all mammalian species. There have been a number of suggestions that other kinds of interferon exist (36), but it remains to be seen whether these and other molecules with antiviral activity will be classified as interferons.