Alpha interferons have been used widely to treat chronic hepatitis C virus infection. These include recombinant interferons, purified natural leukocyte, and lymphoblastoid interferons. Alpha interferon is administered by subcutaneous or intramuscular injection either daily or three times weekly for a period of 6 to as long as 24 months. A wide array of adverse effects of alpha interferon have been described. Several side effects such as fever, headache fatigue, arthralgias, and myalgias are common, especially with the initial injections. These early side effects of interferon are predictable and are encountered in the majority of patients. These may not require dose modification, but can be problematic for a significant proportion of patients. Other adverse events effects may require dose modification or even discontinuation of therapy in 2% to 10% of patients. Neuropsychiatric side effects such as depression and irritability can be most troublesome; their mechanisms are not well understood. Granulocytes, platelets, and red blood cell counts decrease during treatment, but the decreases are usually mild, although they can be dose limiting if cell counts are low initially. Interferon has important immunomodulatory properties, and treatment can induce autoimmune phenomena, the most frequent being autoimmune thyroiditis with either hypothyroidism or hyperthyroidism, especially in predisposed patients. Other autoimmune disease can be aggravated by interferon therapy. Severe and even life-threatening side effects of interferon occur in 0.1% to 1% of patients; these include thyroid, visual, auditory, renal, and cardiac impairment, and pulmonary interstitial fibrosis. Some of these side effects may be irreversible. Higher doses of interferon (above 5 million units three times weekly) cause higher rates of adverse events than standard doses. Contraindications to alpha interferon have been recognized.