Enzyme systems responsible for the novel metabolic pathway of foreign mercaptans leading to the formation of methylsulfonyl metabolites were investigated in rat tissues. The first step was shown to be S-transmethylation. Tetrahydrofurfuryl mercaptan was methylated to its methyl sulfide by liver homogenates in the presence of S-adenosylmethionine. The activity was highest in liver, followed by kidney and small intestine. The hepatic activity was located exclusively in microsomes. The apparent Michaelis constants were 2.5×lO-4M for the acceptor substrate and 1.0×l0−4M for S-adenosylmethionine. The activity was completely inhibited by p-chloromercuriben-zoate, p-chloromercuribenzenesulfonate or HgCl2, whereas it was enhanced by GSH, cysteine or ascorbate.