Effect of cadmium (1 mg/kg body weight) and ethanol (2 g/kg body weight) exposure, alone as well as in combination, on essential trace metal homeostasis, lipid peroxidation and antioxidant defense enzymes in various regions of the adult rat brain was investigated. It was observed that cadmium when administered along with ethanol accumulated significantly in corpus striatum (3.5 fold) and cerebral cortex (3.0 fold) compared to the cadmium treated group. The ethanol induced accumulation of cadmium led to significant depletion in the levels of essential trace metals like zinc and copper in these regions of the brain. Further, cadmium or ethanol alone did not show any significant effect on lipid peroxidation and antioxidant defense enzymes in any of the regions of the adult brain but when given in combination, caused a significant increase in lipid peroxidation and markedly decreased the activities of antioxidant defense enzymes like glutathione peroxidase, superoxide dismutase and catalase particularly in corpus striatum and cerebral cortex. Structural alterations produced by increased lipid peroxidation after cadmium and ethanol co-exposure may have profound effect on the activities of membrane bound enzymes and hence may lead to functional impairment. The results of the present study imply that ethanol renders the adult brain more susceptible to the neurotoxic effects of cadmium. Corpus striatum and cerebral cortex are more vulnerable to the toxic effects of cadmium under the influence of ethanol than other regions of the brain.