Slow potentials were recorded from the anterior cortex of rats during discrimination conditioning and the effects of various doses of d-amphetamine on these responses were examined. In the discrimination paradigm one tone (Sd) was followed at three see after the onset by food reinforcement while another tone (S delta) indicated that no reinforcement would follow. Slow potential (SP) responses were measured during the three-sec period following onset of the stimulus. For the first several training sessions the SP responses demonstrated a phase of generalization during which responses were the same to both stimuli. Thereafter, the responses to Sd were significantly greater than responses to S delta. d-Amphetamine produced a dose-related depression of SP responses to the reinforced stimulus in doses of 0.25 to 2.0 mg/kg. The effect of amphetamine on SP responses to S delta was biphasic; the lower doses (0.25 and 0.5 mg/kg) enhanced responses, no change was seen after 1.0 mg/kg and the high dose (2.0 mg/kg) depressed responses. This study demonstrates that the rat develops differential slow potential responses to reinforced and nonreinforced stimuli in a discrimination paradigm and that d-amphetamine produces a differential and dose-related alteration of these SP responses. It is suggested that the actions of amphetamine may be produced through interference with mechanisms of discrimination, by an effect on subcortical activating systems involving norepinephrine, and/or by activation of inhibitory dopamine receptors on cortical neurons.