The purpose of this observational study was an assessment of the incidence and types of serious psychiatric adverse events (SPAE) associated with the interferon-α (IFN-α) plus ribavirin (RV) therapy in chronic hepatitis C (CHC) patients with compensated liver function and without psychotic or bipolar disorder, without substance abuse or an organic brain disorder at the enrollment. Method. SPAE were defined as psychiatric consequences of IFN-α+RV therapy that resulted in discontinuation of the therapy, psychiatric hospitalisation or initiation of chronic psychiatric disorders. Results. A group of 273 patients (144 males and 129 females aged 18-69 years, mean 41) was prospectively observed. Psychiatric assessment prior to the therapy was done in 240 patients (88%). Recombinant IFN-α was used in 89 patients and 184 were treated with pegylated IFN-α. Overall SPAE were present in ten patients (3,7% of the sample). Eight of them received recombinant IFN-α (Fisher's exact test: p<0,01). One suicidal attempt and two cases of psychotic disorders occurred. Mixed states prevailed among serious affective disorders induced with the IFN-α+RV therapy. Premature cessation of the therapy due to SPAE occurred significantly more often in patients treated with recombinant IFN-α than in those treated with pegylated IFN-α (four vs none; Fisher's exact test: p=0,01). Conclusions. SPAE in CHC patients on the IFN-α+RV therapy arise rarely. However, potentially severe psychiatric consequences of the treatment in some patients point to necessity of psychiatric monitoring during the therapy. Treatment with pegylated IFN-α may be associated with less SPAE than treatment with recombinant IFN-α in CHC patients.