Altered severity of necrosis or a shift in location of certain drug-induced renal cortical lesions have been observed following pretreatment with sulf-hydryl-containing or glutathione-depleting compounds. Cephaloridine-induced outer cortical necrosis undergoes a striking shift to inner cortical necrosis in animals pretreated with cysteine or DDT; the histologic changes are species or strain dependent. These observations implicate an as yet undefined role for sulfhydryl-containing compounds in the pathogenesis of drug-induced renal disease. The histologic shift in necrosis may result from selection of a different population of nephrons (juxtamedullary rather than cortical) or from a shift to a more distal portion (pars recta) of the same nephron population. We propose to resolve this question by microdissection, enzyme histochemistry and/or urinary enzyme assay and to extend our investigations to nephrotoxic lesions or other pathogenesis such as HgCl2 lesions.