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OBJECTIVE: Neuropsychiatric symptoms are commonly associated with chronic hepatitis C virus infection, its sequelae, and its treatment. In particular, interferon, a primary component of treatment for chronic hepatitis C, has been strongly associated with depressive symptoms. This review summarizes current knowledge about the etiology, course, and treatment of neuropsychiatric problems associated with hepatitis C and interferon alpha (IFN-α) treatment. METHOD: Studies were identified by computerized searches, and further references were obtained from bibliographies of the reviewed articles. RESULTS: Chronic infection with the hepatitis C virus is a common and growing problem, often affecting persons with psychiatric and substance use problems. Although changes in cognition, mood, and personality have been described in association with hepatitis C and with IFN-α treatment, there has been little systematic study of these changes. CONCLUSIONS: Psychiatrists should become familiar with the clinical spectrum associated with hepatitis C virus infection as well as the neuropsychiatric symptoms related to hepatitis C and IFN-α treatment. More studies are necessary to define the neuropsychiatric syndromes associated with this population and to find possible effective treatments. Furthermore, research is needed so that patients with psychiatric problems are not excluded from effective treatments for this growing medical problem.