The mesolimbic dopamine (DA) system was lesioned by the injection of 6-hydroxydopamine into the nucleus accumbens or ventral tegmental area of rats. The rats were then examined in a photocell apparatus for their response to injection with the enkephalin analogue, D-Ala2-Met5-enkephalinamide (DALA), into the nucleus accumbens. Rats with DA lesions showed a significantly greater increase in photocell counts in response to DALA than did sham-lesioned animals. The potentiated motor response was dose-related, and rats having the greatest depletion of DA in the nucleus accumbens showed the greatest behavioral response to DALA. It was concluded that chronic impairment of dopaminergic innervation to the nucleus accumbens results in an enhanced response to DALA injected directly into the nucleus accumbens.