Abstract. Three different types of cardiovascular sequelae attributed to interferon therapy have been reported: arrhythmia, ischaemic heart disease and cardiomyopathy. We evaluated the left ventricular ejection fraction (LVEF) during alpha interferon therapy (3 MU administered subcutaneously three times a week for 6 months) in 11 patients with chronic viral hepatitis. LVEF was within the normal range in all patients (mean value ± SD 64.6 ± 10.7%) before interferon was started, but decreased after 1 month of therapy (mean value± SD 59.7 ± 8.3%) (P= 0.015). An LVEF reduction of more than 10% was observed in five of the 11 patients. Three months after therapy was stopped, nine of the 11 patients showed an LVEF close to the pre-treatment level (mean value ± SD 62.1 ± 8.3%). In our patients with chronic C hepatitis, low subcutaneous doses of interferon alpha often decreased the LVEF. It is not clear whether this finding is due to the direct effect of interferon on cardiac cells, or to the peripheral vascular effects of the drug. As LVEF reduction could be critical in patients with previously reduced myocardial contractility, our results further highlight the need for careful cardiac analysis before starting interferon therapy.