The behavioral effects of bilateral N-methyl-D-aspartate (NMDA) lesions of the core and medial shell subregions of the nucleus accumbens were evaluated in rats. Body weight was monitored for 2 weeks following surgery. Locomotor activity and open field behavior were recorded 1 week after surgery. The core-lesion group had difficulty recovering from the lesion and had significantly lower weights throughout the experiment. The shell-lesion group had normal recovery and weighed significantly more than controls over the course of the experiment. In the activity cage test, the core-lesion group was hyperactive when compared to controls and to the shell-lesion group. Activity of the shell-lesion group was similar to that of their sham-controls. Three weeks postlesion, the core-lesion group was still significantly more active. In the open field test, peripheral locomotion scores were significantly higher in the core-lesion group when compared to their controls, whereas the scores of the shell-lesion group were similar to controls. In the other open field measures, both lesion groups were hyperactive; however, the scores of core-lesion group were significantly higher than those of the shell-lesion group on all measures. Histological analysis indicated small, discrete areas of damage within the core or medial shell accumbens regions. These preliminary results suggest that these two subregions can be behaviorally differentiated.