In the present experiment, the effects of neurotoxic lesions (quinolinic acid) of the dorsolateral or dorsomedial striatum were investigated on a simple instrumental discrimination task (CS+/CS-). Rats with lesions of the dorsolateral striatum were found to be impaired in the acquisition of this task, as compared to rats with either dorsomedial striatal or sham lesions. Furthermore, dorsolateral striatal lesioned animals had significantly lower levels of responding across the course of discrimination training, as assessed both by overall rate of response during CS+ presentations and number of CS+ trials without a response, despite having shown levels of responding during variable interval training that did not differ from that of sham lesioned animals. In contrast, animals with lesions of the dorsomedial striatum did not show an impairment in acquisition of the present task, but had slightly higher rates of responding during CS- presentations. It is argued that the poor acquisition and low response rates observed in animals with dorsolateral striatal lesions reflect a failure in stimulus-response learning, while the performance of animals with dorsomedial striatal lesions may have been the result of an increase in overall activity rate.