Studies on the replication of adenovirus DNA were initiated more than two decades ago and quickly led to a novel displacement model for DNA replication (Sussenbach et al. 1972). These studies were mainly performed using intact infected cells or isolated nuclei. It was only after the development of a system to study replication in vitro (Challberg and Kelly 1979) that detailed information could be obtained about the protein-priming mechanism for initiation and about the replication proteins. The last decade has been characterized by the discovery of transcription factors as participants in initiation (Nagata et al. 1982; Pruijn et al. 1986), by complete reconstitution of the system with purified recombinant proteins, and by structural information on some of the replication proteins. After the previous review in this series (Sussenbach and Van der Vliet 1983), several reviews on adenovirus replication have appeared (Kelly1984; Campbell 1986; Van der Vliet et al. 1988; Challberg Kelly 1989; Stillman 1989; Hay and Russell 1989; Van der Vliet 1990, 1991; Salas 1991; De Pamphilis 1993a).