Recent neuroimaging studies have shown that several prefrontal regions play critical roles in inhibiting activation of limbic regions during voluntary emotion regulation. The present study aimed to confirm prior findings and to extend them by identifying the frontal neural circuitry associated with regulation of peripheral physiological responses during voluntary emotion suppression. Ten healthy female subjects were presented with affectively positive, neutral, and negative pictures in each of an Attending and Suppression task. Regional cerebral blood-flow changes were measured using 15O-water positron emission tomography, and autonomic (heart rate: HR, skin conductance response: SCR) and endocrine (adrenocorticotropic hormone: ACTH) indices were measured during both tasks. The left amygdala and the right anterior temporal pole were activated during the Attending task, whereas activation was observed in the left lateral prefrontal cortex (LPFC), including the adjacent medial prefrontal cortex (MPFC), and medial orbitofrontal cortex (MOFC) during the Suppression task. In the Attending task, activation in the amygdala and MOFC positively correlated with magnitudes of the SCR and ACTH responses. Emotion suppression elicited enhancement of SCR and the strength of the effect positively correlated with activation in the MOFC. These results suggest that the MOFC plays a pivotal role in top-down regulation of peripheral physiological responses accompanying emotional experiences.