Experimental manipulations that compromise the medial septal area consistently and selectively impair working memory. The electrophysiological and pharmacological properties of medial septal neurons have been studied extensively, but the relation between medial septal neuronal activity and ongoing behavior has not been systematically analysed. Working memory was assessed in a continuous conditional discrimination task, and behavioral performance was correlated with medial septal single unit activity. Operant performance and the activity of rhythmically active neurons were continuously monitored during a 90 min test session, and peri-event time histograms of unit activity were constructed around relevant task events. Rats received intraperitoneal injections of either saline or ethanol (0.75 g/kg) 5 min before testing. Of the 52 medial septal neurons recorded under saline conditions, approximately 80% had significant behavioral correlates. Thirty-five per cent of these neurons were selectively activated at the time of the response and 65% at the time of the reward. Response-related activity was not selective for responses to the right or left lever, or to a particular type of trial, but in 61% of the cases was correlated with the accuracy of the response. In ethanol-treated rats, working memory was impaired, single unit activity was disrupted, and the behavioral correlates were less frequent and robust, especially the response-related correlates that were accuracy-sensitive. The results suggest that the medial septal area is involved in guiding accurate responses and processing rewards, and may contribute to the ethanol-induced impairments in working memory.