Evidence for the existence of human hepatitis agents besides HAV and HBV is compelling. Transmitted predominantly by transfusion and percutaneous inoculation, the type of NANB hepatitis encountered most frequently is epidemiologically similar to type B hepatitis. NANB hepatitis accounts for more than 90% of TAH, but can be transmitted by nonpercutaneous routes as well. Approximately 15 to 30% of sporadic hepatitis cases are attributable by serologic exclusion to NANB hepatitis agents, and, in addition, there is an epidemic form of NANB hepatitis that resembles hepatitis A epidemiologically in its transmission by the enteric route. Clinical features of the predominantly percutaneously transmitted forms of NANB hepatitis are similar to those of hepatitis B, but tend to be less severe during acute illness, on the one hand, but to lead more frequently to chronic hepatitis, on the other; 40 to 60% of patients with TAH have chronic elevations of aminotransferase activity, often in an episodic, fluctuating pattern. CAH can be identified histologically in a majority of patients with chronic NANB TAH. Despite a relatively quiescent course, progression of such chronic cases may be quite insidious; cirrhosis occurs in 10 to 20% of patients with chronic hepatitis after acute TAH. The frequency of chronic liver disease after nonpercutaneously acquired sporadic NANB hepatitis tends to be lower, on the order of 10% or less, and chronic hepatitis has not been recorded after the epidemic type of NANB hepatitis. Evidence supports the existence of an asymptomatic chronic NANB hepatitis carrier state that is several-fold more frequent than the chronic HBV carrier state. Neither viruses nor virus markers have been described that fulfill accepted criteria reproducibly for a specific causal association with NANB hepatitis; on the other hand, evidence suggests (but does not prove) the existence of two different blood-borne NANB hepatitis agents and, in addition, an enterically transmitted NANB hepatitis agent. Effective therapy for and immunoprophylaxis against NANB hepatitis are lacking. Until specific screening tests are developed, interim screening based on indirect, nonvirus-specific tests may be the only practical approach to minimizing the frequency of NANB hepatitis after transfusion. Identification of virus-specific serologic markers remains a high priority.