ABSTRACT The effect of 16 different genes (rad) conferring radiation sensitivity on chemically induced reversion in the yeast Saccharomyces cerevisiae was determined. The site of reversion used was a well-defined chain initiation mutant mapping in the structural gene coding for iso-1-cytochrome c. High doses of EMS and HNO2 resulted in decreased reversion of cyc1-131 in rad6, rad9 and rad15 strains compared to the normal RAD+ strains. In addition, rad52 greatly decreased EMS reversion of cyc1-131 but had not effect on HNO2-induced reversion; rad18, on the other hand, increased HNO2-induced reversion but did not alter EMS-induced reversion. When NQO was used as the mutagen, every rad gene tested, except for rad14, had an effect on reversion; rad6, rad9, rad15, rad17, rad18, rad22, rev1, rev2 and rev3 lowered NQO reversion while rad1, rad2, rad3, rad4, rad10, rad12 and rad16 increased it compared to the RAD+ strain. The effect of rad genes on chemical mutagenesis is discussed in terms of their effect on UV mutagenesis. It is concluded that although the nature of the repair pathways may differ for UV- and chemically-induced mutations in yeast, a functional repair system is required for the induction of mutation by the chemical agents NQO, EMS and HNO2.