In the first experiment, male rats were injected intracerebroventricularly (icv) with either saline, 12.5, 25, 50, or 100 μ g d -Ala 2 -Met 5 -enkephalinamide (ENK). Uncannulated controls were not injected but were handled similarly. The subsequent behavior of each animal was observed by means of a video system, and was recorded automatically with a system of two crossing photocell beams. Quadrant crossing, rearing, and photocell interruptions of the ENK groups decreased initially, but later increased above control levels. Grooming decreased with all doses and head movement decreased with the two highest doses of ENK. Wet-dog shakes were observed for all ENK groups. In the second experiment, icv-cannulated rats were maintained in the activity chambers and injected each morning with icv-saline followed by an ip saline injection 25 min later. They were habituated to the surroundings and injection procedures for 3 days. On the fourth day, half of the 50 rats were injected with 25 μ g ENK in 2.5 μ l, icv, while the other half were injected with saline and returned to their original activity chamber. Half of each group was injected ip 25 min after the icv injection with 5 mg/kg naloxone or saline, and the activity was recorded for about 4 more hr. Four to five rats from each group were treated similarly for the next 3 days. The activity of the ENK-injected group was higher overall than that of the controls. Naloxone reduced the activity of both the ENK-injected and saline-injected rats. Furthermore, the activity of the ENK-treated rats increased over successive days, whereas that of the controls did not. These results suggest that (1) the increased activity was due to the direct effects of ENK, and (2) some naturally occurring activity may involve endorphins.