The DNA polymerase III holoenzyme is a complex, multisubunit enzyme that is responsible for the synthesis of most of the Escherichia coli chromosome. Through studies of the structure, function and regulation of this enzyme over the past decade, considerable progress has been made in the understanding of the features of a true replicative complex. The holoenzyme contains at least seven different subunits. Three of these, alpha, epsilon and theta, compose the catalytic core. Apparently alpha is the catalytic subunit and the product of the dnaE gene. Epsilon, encoded by dnaQ (mutD), is responsible for the proofreading 3'----5' activity of the polymerase. The function of the theta subunit remains to be established. The auxiliary subunits, beta, gamma and delta, encoded by dnaN, dnaZ and dnaX, respectively, are required for the functioning of the polymerase on natural chromosomes. All of the proteins participate in increasing the processivity of the polymerase and in the ATP-dependent formation of an initiation complex. Tau causes the polymerase to dimerize, perhaps forming a structure that can coordinate leading and lagging strand synthesis at the replication fork. This dimeric complex may be asymmetric with properties consistent with the distinct requirements for leading and lagging strand synthesis.