An important group of patients with chronic hepatitis C have normal serum alanine aminotransferase (ALT) levels despite having hepatitis C virus (HCV) RNA detectable in serum. These patients are typically identified after donating blood and being found to be positive for antibody to HCV (anti-HCV). A strict definition of this patient population is needed, which should include presence of anti-HCV, HCV RNA detectable by polymerase chain reaction (PCR), and persistently normal ALT levels. These patients are usually asymptomatic, but almost all have histological evidence of chronic hepatitis on liver biopsy. The liver histological lesions are generally mild, and cirrhosis is rare. The long-term outcome of this group of patients with chronic HCV infection is not known, but the prognosis is probably good. In small, uncontrolled trials of α interferon in this group of patients, end- of-treatment virological responses occurred in approximately 50% and sustained responses 6 to 12 months afterwards in 20%. These rates of response are not very different from those reported in patients with abnormal ALT levels. Importantly, in most studies, serum ALT levels became abnormal during therapy in approximately half of patients, and levels remained abnormal in a proportion after therapy. These findings suggest that α interferon therapy is not usually beneficial and may be harmful in patients with chronic hepatitis C who have normal ALT levels, perhaps as a result of the immunomodulatory actions of α interferon that may alter the balance of host immune reactions and viral replication, which seem to be responsible for the liver injury in chronic hepatitis C.