The ability of a solution of low-vanadium-content (less than 1 ppm) adenosine triphosphate and magnesium chloride (ATP/MgCl2) versus normal saline to improve recovery of function and reduce necrosis of skeletal muscle after severe ischemia was investigated in an in situ autoperfused canine hind limb model. The study consisted of 12 dogs divided into 3 study groups: nonischemic control (NIL) (n = 7 limbs), ischemic (IL) (n = 7 limbs), and ischemic ATP/MgCl2-treated (IATP) (n = 7 limbs). In groups IL and IATP, the limb was reperfused for 3 hours following 4 hours of complete ischemia. In IATP limbs, 200 mumol/kg of ATP/MgCl2 was infused upon reperfusion of the limbs, whereas IL limbs received a similar volume of normal saline at the time of reperfusion. Function was determined by stimulating the deep peroneal nerve and anterior tibial muscle and measuring the resultant isometric twitch contractile force of paw dorsiflexion. Muscle necrosis was evaluated by photographic analysis of sectioned anterior tibial muscle stained with nitroblue tetrazolium dye. ATP/MgCl2 significantly increased functional recovery (p < 0.01) and significantly reduced skeletal muscle necrosis (p < 0.01). This study suggests that ATP/MgCl2 may be useful in reducing the clinical sequelae of severe limb ischemia and reperfusion.