Abstract Psychiatric symptoms during interferon (IFN) therapy for viral hepatitis have been a crucial problem in consultation-liaison psychiatry. However, there have been few studies on psychiatric management for these symptoms and their prognosis. Among 943 patients who were treated with IFN for chronic hepatitis C between 1991 and 1995, 43 patients (4.6%) developed psychiatric symptoms during IFN treatment. Three patients (0.3%), with pre-existing psychiatric disorders showed aggravated symptoms and were excluded from the study. All three patients were able to finish the IFN therapy with psychiatric management. Forty patients (4.2%) manifested psychiatric symptoms induced by IFN. Thirteen patients (1.4%) were diagnosed as anxiety disorder and 21 patients (2.2%) revealed mood disorder with depressive features. There were other psychiatric disorders in six patients (0.6%), including psychotic disorder with delusions/hallucinations in four patients (0.4%), mood disorder with manic features in one patient (0.1%) and delirium in one patient (0.1%). Women developed psychiatric symptoms significantly more than men. Ten of 40 patients (25%) stopped IFN treatment because of manifesting psychiatric symptoms induced by IFN. Twelve patients (30%) required psychiatric treatment for more than 24 weeks after ceasing IFN, and seven patients still had anxiety, insomnia and mild hypothymia at the end of the present study. Statistical analysis revealed that IFN-β therapy and psychiatric manifestations including psychotic symptoms, delirium and manic symptoms were significantly related to long-term psychiatric problems. There are considerable numbers of patients who have required long-term psychiatric management even after cessation of IFN treatment.