In all organisms studied to date, DNA replication is catalyzed by a multi-enzyme complex that unwinds the double helix, primes DNA synthesis, and copies two DNA strands with remarkable speed and accuracy. The physical interactions of proteins within the replication complex help to organize these activities so that two antiparallel strands of DNA are efficiently copied in highly coordinated reactions. The replication machinery of the bacteriophage T7 is particularly well suited for detailed studies of these reactions; the phage performs these essential tasks with only four proteins. We are using x-ray crystallographic methods to investigate the physical basis for the cooperative behaviors of the T7 DNA polymerase, its associated helicase-primase protein, and the T7 single strand DNA binding protein. Crystal structures of these replication proteins complexed to DNA and nucleotide substrates are being determined alone, and in multiprotein complexes representing major components of the T7 DNA replication fork. Despite its simplicity, the phage T7 replication system faithfully mimics many features of the more complex DNA replication processes of higher organisms. This model system offers many advantages for detailed physical and mechanistic studies of the protein interactions and conformational changes that contribute to the fidelity of DNA synthesis, the coupling of nucleotide hydrolysis to DNA unwinding by helicases, and the polymerization of RNA primers for the discontinuous synthesis of the lagging strand of the replication fork. Our high resolution structural studies are beginning to reveal the overall architecture of the T7 DNA replication complex and the flow of substrates and products through this DNA synthesis machine.