In the present study, in vivo voltammetry was used to monitor changes in dopamine levels in the left and right medial prefrontal cortex of rats exposed to mild physical and psychological stress. These were 2 min of tail-pinch and 15 min exposure to cat odour, respectively. Fourteen male Long Evans rats with bilateral carbon fibre recording electrodes were tested on four consecutive days, and records obtained in each medial prefrontal cortex for each stressor. A week later, animals underwent a 20 min restraint stress, with plasma samples taken at 0, 20 and 80 min to determine stress-induced corticosterone responses. It was found that dopamine responses to tail-pinch were significantly longer-lasting in the left hemisphere than in the right, while this asymmetry was not present for the dopamine response to cat odour. Stress-induced dopamine increases elicited by the two stressors were significantly correlated only in the right medial prefrontal cortex. Restraint stress-induced increases in plasma corticosterone were positively correlated with dopaminergic responses to tail-pinch, but were only related to dopamine cat odour responses when individual asymmetries favoured the right medial prefrontal cortex. The data suggest that asymmetric mesocortical dopamine activation depends on the type of stress, and that regulation of dopamine responses to both types of stress is most tightly coupled in the right hemisphere. While neuroendocrine and dopaminergic stress responses are positively linked, this relationship is only asymmetrical for the psychological stressor, suggesting a specialized role for right cortical mechanisms in the integration of emotional and physiological responses to stressful situations. A preliminary report of this work was presented at the Society for Neuroscience meeting in Washington DC, November, 1996.