Spontaneous motor activity was studied following injection of 1, 10 and 50 mug of serotonin (5-HT) into the lateral ventricle of chronically cannulated rats. During the first 15 min, the rats receiving the higher doses of 5-HT showed significant decrements (P less than 0.01) in motor activity compared to saline controls. No activation was observed in either group. After 20 min, no significant differences for any treatment condition compared to saline controls were observed. It is concluded that a principal effect of directly increasing brain 5-HT concentration is to decrease activity. Possible mechanisms for this effect are discussed.