Non-A, non-B hepatitis is a newly recognized disease entity. Although initially described as a transfusion related viral infection, the disease can occur in sporadic, endemic, and epidemic settings. There are no confirmed, reproducible serologic tests for associated antigens or antibodies, but electron microscopy has revealed virus-like particles of different sizes. Nonspecific laboratory tests of hepatic dysfunction, especially alanine aminotransferase, are currently utilized to diagnose non-A, non-B hepatitis in patients and may be used to implicate blood donor carriers of this virus. The existence of an infectious non-A, non-B hepatitis agent and proof of a chronic carrier state in humans have been documented by transmission studies in chimpanzees. Cross challenge studies in chimpanzees, as well as some epidemiologic data, suggest that more than one agent causes non-A, non-B hepatitis.