Arsenic and di-(2-ethylhexyl) phthalate (DEHP) are environmentally ubiquitous and epidemiologically important toxic agents that millions of people are currently exposed to, worldwide. Although the adverse impact due to exposure to either arsenic or DEHP are documented, the toxicological effects of co-exposure to these agents are largely unknown. In this study, exposure to these chemicals was investigated for their effects on ATPase activities in the brain, liver and kidney of rats. Male Wistar rats were exposed daily to 100 mg L -1 arsenic via drinking water and to 100 mg DEHP kg -1 body weight in corn oil either individually or concurrently for 30 days. Toxicity was assessed by evaluating changes in body and organ weights, as well as, Na + /K + -, Ca 2+ -, Mg 2+ -and total ATPase activities in the brain, liver and kidney. Exposure to either arsenic or DEHP resulted in drastic reduction in activities of the enzymes in the compartments investigated, except in the brain where Na + /K + -and Mg 2+ -ATPases had their activities significantly increased. Also, DEHP displayed no effect on the total ATPase and Ca
2+ATPase in the kidney and brain, respectively. Interestingly, co-exposure to these toxicants significantly stimulated the activities of all these enzymes in the brain. In this compartment, combined treatment resulted in an additive interaction between the toxicants and a potentiation effect of arsenic on DEHP with regards to the Na + /K + -ATPase activity and Ca 2+ -ATPase activity, respectively. Our findings demonstrate tissue specific response to combined arsenic and DEHP exposure in rats with the effect on the brain significantly different from other compartments.