Gastric distension activates a cerebral network including brainstem, thalamus, insula, perigenual anterior cingulate, cerebellum, ventrolateral prefrontal cortex and potentially somatosensory regions. Cortical deactivations during gastric distension have hardly been reported. To describe brain areas of decreased activity during gastric fundus distension compared to baseline, using data from our previously published study (Gastroenterology, 128, 2005 and 564). H(2) (15)O-brain positron emission tomography was performed in 11 healthy volunteers during five conditions (random order): (C(1)) no distension (baseline); isobaric distension to individual thresholds for (C(2)) first, (C(3)) marked, (C(4)) unpleasant sensation and (C(5)) sham distension. Subtraction analyses were performed (in SPM2) to determine deactivated areas during distension compared to baseline, with a threshold of P(uncorrected_voxel_level) < 0.001 and P(corrected_cluster_level) < 0.05. Baseline-maximal distension (C(1)-C(4)) yielded significant deactivations in: (i) bilateral occipital, lateral parietal and temporal cortex as well as medial parietal lobe (posterior cingulate and precuneus) and medial temporal lobe (hippocampus and amygdala), (ii) right dorsolateral and dorso- and ventromedial PFC, (iii) left subgenual ACC and bilateral caudate head. Intragastric pressure and epigastric sensation score correlated negatively with brain activity in similar regions. The right hippocampus/amygdala deactivation was specific to sham. Gastric fundus distension in health is associated with extensive cortical deactivations, besides the activations described before. Whether this represents task-independent suspension of 'default mode' activity (as described in various cognitive tasks) or an visceral pain/interoception-specific process remains to be elucidated.