Mutant bacteriophage T4 DNA polymerases exist that appear primarily to reduce the frequency of AT-to-GC transitions when this [antimutator' phenotype is assessed by genetic methods. This observation disagrees with in vitro studies, which indicate that T4 antimutator DNA polymerases have increased proofreading abilities and effectively edit all types of base substitution errors. One explanation that reconciles the apparent in vivo mutational specificity of antimutator DNA polymerases with their biochemical properties is that the in vivo mutational specificity identifies mismatched primer-termini that are corrected less efficiently by the wild-type level of proofreading activity, but are corrected if proofreading is increased.