Although the recognition of hepatitis as an infectious disease dates to antiq uity, the identification of hepatitis B virus (HBV) as one of its important causes was not achieved until the late 1960s. Over the ensuing 10 years, rapid progress was made in the structural and biological characterization of the virus, but its narrow host range and inability to be propagated in cultured cells stymied early efforts to elucidate the molecular details of viral replication. Within the past decade, however, the development of workable animal mod els of HBV infection, together with ongoing advances in molecular genetics, has brought these once-refractory areas into full experimental view. The result has been the revelation of a remarkably intricate life cycle, at each step of which unusual strategies are employed. The replication of viral DNA pro ceeds via reverse transcription of an RNA intermediate, using protein and RNA primers for the generation of the first and second DNA strands. Large fractions of the genome are translated in more than one reading frame; within a frame, proteins from multiple in-phase initiator codons are expressed from overlapping transcripts. The resulting closely related gene products can be posttranslationally processed and assembled into a variety of structures of differing function or subcellular distribution. The elucidation of these and other remarkable features of the life cycle has offered new insights into the evolutionary origins of these viruses, identified potential targets of antiviral therapy, and provided a new conceptual framework for understanding the mechanisms of viral pathogenesis. In this article we review recent progress in the molecular analysis of the hepatitis B viruses, after a brief overview of their biology. Readers with an interest in a fuller accounting of the biological and clinical aspects of HBV infection are referred to several excellent reviews emphasizing these areas (1-6); other reviews emphasizing virologic aspects of HBV have recently been published (7-10).