The history of non-ABC hepatitis is a kaleidoscope of intriguing, but often conflicting and confounding data. Studies of transfusion-associated non-ABC hepatitis are less convincing than they originally seemed. Chimpanzee cross-challenge studies, once the bastion for the theory of multiple NANB hepatitis agents, now have an alternative explanation in the impaired immune response associated with HCV infection and the ability of this agent to reinfect individuals previously assumed to be immune. Nonetheless, there are so many cases of acute and chronic NANB hepatitis that cannot currently be attributed to HCV that it is hard to avoid the implication of at least one, and possibly more, non-ABC hepatitis agents. There are now some transmission studies in small primates to support this contention, though recent chimpanzee transmission studies have been disappointingly negative. As with the hepatitis C virus, the breakthrough in this disease will not come from classic serology or virology, but from molecular biology. Similar molecular approaches to those that elucidated HCV are in progress and are promising in preliminary experiments. It is anticipated that the pace of molecular biology is such that a great deal more will be known about non-ABC in a relatively brief time, and perhaps one or more non-ABC agents will prove to be real and clinically relevant.