The effects of vitamin B6 status and lead (Pb) toxicity on aspects of glutathione (GSH) metabolism in rats were examined in a 2 x 2 factorial experiment. The administration of 2000 ppm Pb as Pb acetate.3H2O significantly (P less than 0.05) increased hepatic GSH levels in rats receiving B6-adequate (+B6) but decreased GSH in rats fed B6-deficient (-B6) diets. The addition of Pb to the +B6 diet also increased hepatic glutathione reductase (GSSG-R) activity. Plasma pyridoxal phosphate (PLP), cystathionine and valine levels were decreased by the -B6 diets independent of the presence of Pb. Plasma arginine, alanine, serine and proline levels were increased by Pb in both -B6 and +B6 groups. Glycine levels were increased in -B6 rats only in the absence of Pb while taurine was decreased by Pb only in +B6 rats. There were significant -B6 x Pb interactions for hepatic GSH, cysteine and GSSG-R as well as plasma valine, glycine and proline. These results suggest an influence of B6 status on Pb-induced changes in hepatic GSH, possibly through its role as a co-factor for enzymes involved in amino acid metabolism.