The discovery of interferon raised hope that an endogenous cellular protein could be developed as a clinically important antiviral agent. Preclinical studies have provided valuable insight into optimal doses and scheduling, toxicities, and possible synergistic interactions of the interferons with other agents. However, as our understanding of the complex role of such agents in the immune system is still incomplete, the rational design of clinical studies remains a significant challenge. Although experience with interferons in controlled clinical trials is limited, the potential exists for many of these agents to emerge as important treatment modalities in malignant, infectious, and immunologic disorders. The major focus of recent clinical studies with human interferon has been the evaluation of recombinant or highly purified interferon-alpha preparations in selected malignant and viral disorders. Interferon-beta, which shares antiviral, antiproliferative, and immunomodulatory properties with interferon-alpha, as well as common cell surface receptors, is at an earlier stage of clinical development.