High titers of interferon were found in serum from 20 (24.4%) of 82 patients with psychosis and from only two (3.1%) of 64 control subjects. Interferon-positive patients were more likely than interferon-negative patients to have had a recent onset or exacerbation of their illness and to be on low-dose or no medication. No interferon was detected in the CSF of 65 patients or 20 control subjects. These findings suggest that there may be immunological abnormalities or viral infections in some patients with psychosis.