Systemic and intracerebroventricular administration of analgesic doses of morphine resulted in large increments of spontaneous multiple unit activity in the periaqueductal gray matter of the awake rat. Intracerebroventricular injection of methionine enkephalin gave analgesia in only 8 of 19 rats, but in all 8, and in no others, increased periaqueductal multiple unit firing was also seen. These findings support the view that the periaqueductal gray matter is actively involved in endogenous mechanisms of analgesia. A striking observation was that enkephalin caused electrographic and behavioral epileptic phenomena in most animals. This observation together with other recent findings suggests that endogenous enkephalin may play some role in epileptogenesis.