Interferons have been studied in animals and man for local and systemic viral infections that are either rare or common. Recent clinical studies in humans with purified or recombinantly derived interferons have demonstrated significant clinical response in rhinovirus common colds, herpetic keratitis, condyloma acuminata, and laryngeal papillomatosis. However, only 40 per cent of published papers with IFN have been appropriately controlled. The toxicity of these newer preparations when administered either topically or parenterally prevents their immediate licensing for general use. The toxic to therapeutic ratio for HuIFN and rIFN appears to be close to one in most clinical situations in which it has been tested. Although interferons have not proved to be the "penicillin" for viruses many thought they would become, basic in vitro work and clinical studies have contributed greatly to our understanding of host defense and immunopathology. Future studies must focus on increasing our understanding of the mechanisms of toxicity, in addition to devising controlled clinical trials with interferon alone or in combination with other antiviral agents. Thus, after 30 years of research on interferons, it would appear our work has just begun.