DNA-damaging agents can stimulate the formation of directed reciprocal translocations in strains of Saccharomyces cerevisiae containing his3 recombinational substrates to generate chromosomal rearrangements. Such agents were compared with those that can stimulate sister-chromatid recombination. We show that chemicals and environmental agents that produce a variety of DNA lesions, including bulky adduct, thymidine dimers, interstrand cross-links, double-strand breaks alkylated bases, can stimulate recombination to yield reciprocal translocations. Of the agents tested, only the alkylating agents methyl methanesulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and a bifunctional agent that causes bulky DNA adducts, 4-nitroquinoline-N-oxide (4-NQO), significantly stimulate sister-chromatid recombination in our assay. Factors that contribute to the stimulation of interchromosomal recombination include strain genetic background and ploidy.