A certain group of patients with chronic hepatitis C have normal serum alanine aminotransferase (ALT) levels, despite the replication of hepatitis C virus (HCV) in infected liver cells and detection of HCV RNA in serum. These patients are usually asymptomatic and are discovered fortuitously, generally after a volunteer blood donation. A standard definition for this group of patients is obviously needed, which should include the presence of anti-HCV, detectable serum HCV RNA by polymerase chain reaction and persistently normal ALT levels. These patients have minimal or mild necroinflammatory lesions in liver tissue specimens and cirrhosis is rare. The natural course of the disease in this epidemiologic setting is unknown, but the progression is probably good. Alpha-interferon has been administered in small pilot studies and three controlled studies. Overall, the end of treatment response was 35% and the sustained virologic response 15%. These response rates are similar to those reported in patients with elevated ALT levels. More important, serum ALT levels became abnormal during therapy in 47% of the patients and levels remained elevated in some patients after therapy. Prospective studies on the long-term natural history of HCV infection in this setting are needed and well designed randomized controlled trials are necessary to determine whether these patients would benefit from IFN or a combination treatment with ribavirin regimen. Currently, there is no rationale to treat these patients.