Bacteriophage T4 initiates DNA replication from specialized structures that form 
in its genome. Immediately after infection, RNA-DNA hybrids (R-loops) occur on 
(at least some) replication origins, with the annealed RNA serving as a primer 
for leading-strand synthesis in one direction. As the infection progresses, 
replication initiation becomes dependent on recombination proteins in a process 
called recombination-dependent replication (RDR). RDR occurs when the 
replication machinery is assembled onto D-loop recombination intermediates, and 
in this case, the invading 3' DNA end is used as a primer for leading strand 
synthesis. Over the last 15 years, these two modes of T4 DNA replication 
initiation have been studied in vivo using a variety of approaches, including 
replication of plasmids with segments of the T4 genome, analysis of replication 
intermediates by two-dimensional gel electrophoresis, and genomic approaches 
that measure DNA copy number as the infection progresses. In addition, 
biochemical approaches have reconstituted replication from origin R-loop 
structures and have clarified some detailed roles of both replication and 
recombination proteins in the process of RDR and related pathways. We will also 
discuss the parallels between T4 DNA replication modes and similar events in 
cellular and eukaryotic organelle DNA replication, and close with some current 
questions of interest concerning the mechanisms of replication, recombination 
and repair in phage T4.