We used positron emission tomography (PET) to monitor the regional cerebral blood flow (rCBF) as an index of brain activity in regions proposed to participate in affective-motivational and cognitive-evaluative dimensions of pain during anticipation of a noxious stimulation. Specifically we were interested in the anterior cingulate cortex (ACC), the ventromedial prefrontal cortex (VMPFC) and the periaqueductal grey (PAG). Anticipating an unpredictable and unlearned pain stimulus activated the right ACC, the VMPFC and the PAG while anticipating a learned pain-stimulus resulted in a decreased activity in the ACC and the VMPFC. These patterns are compatible with two facets of affect-laden cognitive coping: alertness and attention-distraction. The right-preponderant expression of the changes in the ACC supports the hypothesis of a preferential role of the non-dominant hemisphere in negative emotional processing. The data demonstrate an anticipatory coping mechanism and illustrate a neurophysiological process underlying the modulation of attention to pain.