The influence of methionine supplementation on the efficacy of common antidotes to lead poisoning, calcium disodium ethylenediaminetetraacetate (CaNa_2EDTA) and D-penicillamine (DPA), was investigated in rats. The animals were given lead acetate (0.1% in drinking water) for 12 weeks and thereafter treated with CaNa_2EDTA, DPA (0.3mmol/kg, intraperitoneally), DL-methionine (1.34 mmol/kg, intragastrically), or the combination of a chelating agent and methionine for 3 days. While chelating agents enhanced the urinary excretion of Pb, methionine increased the fecal excretion of Pb significantly. Treatment with the combination of a chelating agent and methionine did not potentiate the effect of each antidote. However, methionine supplementation increased the efficacy of both chelating agents in reducing the hepatic and renal Pb burden but not the blood Pb level. The Pb-induced inhibition of blood δ-aminolevulinic acid dehydratase activity and the increase in urinary excretion of δ-aminolevulinic acid were reversed to a certain extent by CaNa_2EDTA, DPA, and methionine but the combination did not improve their individual performances. The beneficial effects of methionine may be attributed to its ability to increase the bioavailability of glutathione (GSH), useful in chelating Pb and counteracting the toxic effects, as evidenced by restoration of the Pb-induced decrease in hepatic GSH level by treatment with methionine. Methionine may be useful as a supportive therapy in chelation of Pb. (c)1989 Academic Press. Inc. The influence of methionine supplementation on the efficacy of common antidotes to lead poisoning, calcium disodium ethylenediaminetetraacetate (CaNa_2EDTA) and D-penicillamine (DPA), was investigated in rats. The animals were given lead acetate (0.1% in drinking water) for 12 weeks and subsequently treated with CaNa_2EDTA, DPA (0.3 mmol / kg, intraperitoneally), DL-methionine (1.34 mmol / kg, intragastrically), or the combination of a chelating agent and methionine for 3 days. While chelating agents enhanced the urinary excretion of Pb , methionine increased the fecal excretion of Pb significantly. Treatment with the combination of a chelating agent and methionine did not potentiate the effect of each antidote. However, methionine supplementation increased the efficacy of both chelating agents in reducing the hepatic and renal Pb burden but not the blood Pb level. The Pb-induced inhibition of blood δ-aminolevulinic acid dehydratase activity and the increase in urinary excretion of δ-aminole The beneficial effects of methionine may be attributed to its ability to increase the bioavailability of glutathione (GSH), useful in chelating Pb and counteracting the toxic effects, as evidenced by restoration of the Pb-induced decrease in hepatic GSH level by treatment with methionine. Methionine may be useful as a supportive therapy in chelation of Pb. (c) 1989 Academic Press. Inc.