The effects of unilateral cortical spreading depression (CSD) on feeding, drinking and other behaviors were studied in rats. CSD waves were elicited by a microinjection of KC1 solution through an implanted cannula. The animal's behavior and slow potential changes (SPC) accompanying CSD were then simultaneously monitored for 20 min. Intensive face grooming was observed while the CSD wave-front propagated across the sensorimotor cortex. Animals commenced their first feeding or drinking shortly after the invasion of the negative SPC into the frontal cortex of Krieg's area 6 and 10 [14] had reached its maximum height. A two-way switching effect between the first feeding or drinking and quiescence (freezing) and a close relationship between their onsets were observed. The results are discussed specifically in relation to cortico-hypothalamic pathways.