The neuroprotective effect of the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was tested in a 2-vessel occlusion model in rats. The post-ischemic core temperature was carefully monitored for 24 h. After 7 days of survival, the viable CA1 neurons were counted in an 8-OH-DPAT (125 microg/kg/h) and vehicle-treated group using the optical fractionator method. The vehicle-treated ischemic rats had a median number of dorsal CA1 neurons of 49,900 whereas the 8-OH-DPAT-treated ischemic rats had a significant lower median number of dorsal CA1 neurons 105,200 (P=0. 018). 8-OH-DPAT significantly lowered the core temperature compared to the vehicle-treated group during the 24-h post-ischemic period. Hypothermia is proposed as a possible explanation of the neuroprotective effect of 8-OH-DPAT.