The bacteriophage T4 rnh gene encodes T4 RNase H, a relative of a family of flap endonucleases. T4 rnh null mutations reduce burst sizes, increase sensitivity to DNA damage, and increase the frequency of acriflavin resistance (Ac^r) mutations. Because mutations in the related Saccharomyces cerevisiae RAD27 gene display a remarkable duplication mutator phenotype, we further explored the impact of rnh mutations upon the mutation process. We observed that most Ac^r mutants in an rnh⁺ strain contain ac mutations, whereas only roughly half of the Ac^r mutants detected in an rnh strain bear ac mutations. In contrast to the mutational specificity displayed by most mutators, the DNA alterations of ac mutations arising in rnh and rnh⁺ backgrounds are indistinguishable. Thus, the increase in Ac^r mutants in an rnh background is probably not due to a mutator effect. This conclusion is supported by the lack of increase in the frequency of rI mutations in an rnh background. In a screen that detects mutations at both the rI locus and the much larger rII locus, the r frequency was severalfold lower in an rnh background. This decrease was due to the phenotype of rnh rII double mutants, which display an r⁺ plaque morphology but retain the characteristic inability of rII mutants to grow on  lysogens. Finally, we summarize those aspects of T4 forward-mutation systems which are relevant to optimal choices for investigating quantitative and qualitative aspects of the mutation process.