Chronic administration of disulfiram (DS) to rats was found to affect glutathione (GSH) metabolism. Glutathione was measured in the rat brain following DS administration. Reduced glutathione was decreased significantly (1.52 +/- 0.3 mumol/g; p < 0.001), with a concomitant increase in oxidised glutathione (GSSG) content (0.12 +/- 0.013 mumol/g; p < 0.001) in the brain as a consequence of DS treatment. However, total glutathione (GSH + GSSG) content of the experimental group did not show any appreciable change. Similar changes were observed in the liver following chronic DS treatment. Brain glutathione reductase (GR) activity was found to be significantly depleted (100 +/- 0.16 mumol/min/mg protein), but glutathione peroxidase (GP) activity was not affected in rats chronically treated with DS. It is reported that the treatment with DS decreases the GSH content, with a concomitant increase in GSSG level, and perturbs the GSH/GSSG redox status, inducing an oxidative stress on the brain. Glutathione reductase implicated in maintaining GSH/GSSG homeostasis by replenishing GSH is also affected by DS potentiating the oxidative damage of the tissue. This effect of DS on glutathione metabolism in the brain would explain some of its known neurotoxic effects.