We studied the effectiveness of serotonin la agonist(8 OH DPAT) on the 24 hour ionic lesion volume produced by permanent occlusion of the middle cerebral artery(MCAo) in rats. A 4-hour intravenous infusion of 30pmg/ kg/hr of 8 OH DPAT were given starting at 10 minutes after occlusion. Tissue concentrations of Na, K. and water at infarct and peri-infarct zone were measured by atomic absorption spectroscopy and by wet-dry weight measurements 24 hours after occlusion. Compared with vehicle treatment, 8 OH DPAT treatment reduced tissue water accumulation by 10% and 55% in the frontopyriform cortex(L1) and frontoparietal cortex(L2), sodium accumulation by 20% at L1 and 47% at L2 potassium loss by 24% at L1 and 44% at L2, cell volume fraction loss by 24% at L1 and 47% at L2. Finally the treatment reduced overall lesion volume by about 37%. All these changes were statistically significant at p <0.05. Our findings suggest strongly that 8 OH DPAT is neuroprotective in the rat MCAo model of focal cerebral ischemia.