A bilateral microinjection into the anterior hypothalamus of 5,6-dihydroxytryptamin (5,6-DHT), a substance that lesions serotonin (5-HT)-containing neurons, caused a rise in the body temperature of the rat. The anatomical sites were the same as those at which 5-HT given in the same dose range (1.25-2.5 mug) evoked a similar hyperthermia. When exposed for one hour to a temperature of either 35 degrees C or 8 degrees C, the rats were not able to defend against the heat or cold, respectively. The magnitude of this thermoregulatory deficit depended upon the dose of 5,6-DHT given as well as the site of injection. A partial recovery from the warmth deficit was evident 13-17 days following the 5,6-DHT microinjection. Food and water intakes were also suppressed significantly and body weights declined concomitantly. These results provide additional evidence to support the view that a serotonergic mechanism in the hypothalamus is involved in both thermoregulation and the control of ingestive behavior.