Little is known about the cerebral representations of visceral sensations in humans. Using functional magnetic resonance imaging (fMRI), we mapped the cortical areas of the human brain that were activated by mechanical stimulation of the esophagus in 5 healthy volunteers. Stimulation probes were placed into the distal part of the esophagus and inflated to produce a local distention. The cerebral activation pattern was related to the strength and quality of the stimulus. The weakest stimulus accompanied by a well-localized albeit weak retrosternal sensation activated only the parietal opercular cortices, probably including the secondary somatosensory cortex (SII). Additional activation of the primary sensorimotor cortex (SI) at the level of the face and mouth representation as well as of the right premotor cortex was found during repetitive distention of the esophagus at 0.5 Hz. Repetitive stimulation at 1 Hz additionally activated the insulabilaterally. The strongest distention stimulus, which caused a painful retrosternal sensation, resulted in an activation of the anterior cingulate cortex. Our findings demonstrate that SII is the primary cortical target of visceral afferents originating in the esophagus. Limbic structures become engaged when the visceral senstion is unpleasant or painful.