Recently, we found interferon in the sera of patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, and Sjögren's syndrome. In this study, we surveyed a variety of other immunologically mediated diseases. We did not find interferon in the sera of patients with Wegener's granulomatosis, sarcoidosis, infectious mononucleosis, minimal change nephritis, kidney transplants, myasthenia gravis, or uveitis, but we did find this protein in the sera of patients with active systemic and cutaneous vasculitis. Attempts to characterize the interferon in the sera of patients with systemic lupus erythematosus and vasculitis revealed that antibody to alpha (leukocyte) interferon, but not to beta (fibroblast) interferon, partially or completely neutralized the antiviral activity. The failure of antibody to alpha interferon to completely neutralize the antiviral activity in certain specimens and the lability of the antiviral activity in some specimens to pH 2.0 treatment both suggest that more than one type of interferon was present.