Cortical spreading depression (CSD) was elicited by focused ultrasonic irradiation (800 kHz) of exposed cerebral cortex in anesthetized rats. With the acoustic output of 0.64 W at the probe-tissue contact (3 mm in diameter), CSD was elicited after 28-sec irradiation in normothermic rats. Reduction of cortical temperature to 31 degrees C increased the threshold irradiation time to 82 sec on the average. Ten- to thirty-sec heating of cerebral cortex with a thermode elicited CSD when surface temperature exceeded 47 degrees C. Histological examination of the cortical areas exposed to threshold irradiation revealed a central coagulation lesion surrounded by edema. It is concluded that the ultrasonic irradiation elicits CSD by dissipated heat. Differences in threshold duration of irradiation in hypothermic and normothermic rats were used to compute the threshold temperature which had to be exceeded in the critical volume of cortex in order to start CSD.