Serially propagated fibroblast clones were treated with 25-mM methionine and a thioguanine resistance assay was performed at each passage to measure mutagenesis at the HGPRT locus. The spontaneous frequency of thioguanine resistant mutants before treatment was less than 5 X 10(-6) in four clones and 22 X 10(-6) in one clone. These values dropped 10- to 100-fold and remained so until the methionine was withdrawn, then returned to, or overshot, the initial values. It is proposed that these fibroblasts, unlike their previously described RSV-transformed counterparts, possess a repair enzyme capable of an adaptive response to S-adenosylmethionine, the metabolite thought to be responsible for methionine mutagenicity in vivo.