Previous work in our laboratory has found that whereas medial septal lesions impaired an operant left-right delayed alternation task in rats, the lesion also facilitated the performance of rats on a cued go/no-go discrimination task with a delay between the cue and the required response. These findings suggested to us that the medial septal lesions impaired "response" working memory, which in turn led to a compensatory enhancement of attention to stimulus cues. If this hypothesis is true, then the lesions should impair a go/no-go task based on "response" working memory. The current experiment tested this hypothesis. Rats (12 with medial septal lesions and 12 with sham operations) were tested on a discrete trial operant go/no-go response alternation task. The rats were first tested for 20 days without a delay contingency, followed by 35 days of testing with a 15-s delay between "go" and "no-go" trials. Both groups became proficient at the task under nondelay conditions and their terminal performance (averaging about 85% correct) did not differ. However, under delay conditions the performance of the lesioned rats was significantly impaired compared to the controls. As the go/no-go task does not require a spatial discrimination, the best explanation for our findings is that the lesions impaired response working memory.