Human skin fibroblasts, isolated in vitro, from donors carrying the Mediterranean variant of glucose-6-phosphate dehydrogenase, exhibit a sharp decrease of hexose monophosphate shunt and NADPH/NADP+ ratio when compared to the fibroblasts from normal donors. This behavior is coupled to an increase of the resistance to cell death and growth inhibition induced by benz(a)pyrene, whose activation proceeds through the NADPH-dependent arene oxide formation. No differences were observed in the toxic effects of methylnitrosourea, a carcinogen that does not need metabolic activation, on normal and variant fibroblasts.