Oxygen free radicals may be implicated in the pathogenesis of ischemia-reperfusion damage. It is known that 2-chloroadenosine (2-CADO) has neuromodulatory effects and prevents the neuronal damage seen in the period of postischemia reperfusion. However, direct effects of 2-CADO on lipid peroxidation have not been investigated previously. The attack on the cell membrane by free radicals leads to lipid peroxidation, which can be assayed by the malondialdehyde (MDA) level. The aim of this study was to determine the effect of 2-CADO therapy on lipid peroxidation in experimental forebrain ischemia and postischemia reperfusion in Mongolian gerbils. Cerebral ischemia was induced by a bilateral 30-mm occlusion of the common carotid arteries, 2-Chloroadenosine (0.6 mg/kg, IV) was administered 5 min subsequent to ischemia. Ischemia was followed by reperfusion for 30 min. The MDA level was measured by the thiobarbituric acid (TEA) test. Bilateral carotid artery occlusion for 30 min in gerbils resulted in no significant change in MDA level in the brain. The MDA level was higher in postischemia reperfusion than in the ischemic group. 2-Chloroadenosine treatment did not change the MDA level in the ischemic period. However, the MDA level recovered significantly upon 2-CADO therapy during reperfusion following ischemia. These results suggest that 2-CADO may offer some degree of protection against oxidative stress in cerebral ischemia-reperfusion damage. Copyright (C) 1996 Elsevier Science Inc.