OBJECTIVES: During gastric distension in hypersensitive functional dyspepsia (FD), activation was found in somatosensory cortex (SI/SII) and ventrolateral prefrontal cortex (vlPFC) but, contrary to controls, not in pregenual anterior cingulate (pACC). The aims of this article were to study (i) cortical activations and deactivations during distension and sham compared with baseline in FD, regardless of sensitivity status; (ii) differences in brain activity between health and FD during "no distension" conditions; and (iii) the relationship between anxiety and brain activity in FD. METHODS: Brain H(2)(15)O-PET was performed in 25 FD patients (13 hypersensitive) during three conditions: baseline, distension at discomfort threshold, and sham. Brain activity was compared against healthy controls using SPM2. RESULTS: Discomfort threshold was lower; sensation scores in all conditions were higher in patients than controls. (i) Activations were similar to controls, except for a lack of pACC activation during distension in FD. Patients showed no dorsal pons and amygdala deactivation during distension and sham, respectively. (ii) Comparing baseline or sham activity showed the following differences: higher activity in SII/SI, insula, midcingulate (MCC), dorsolateral and ventrolateral PFC in controls; and higher activity in occipital cortex in FD. Differences in left lateral PFC were specific to sham. (iii) Anxiety correlated negatively with pACC and MCC and positively with dorsal pons activity. CONCLUSIONS: FD patients failed to activate pACC, to deactivate dorsal pons during distension, and to deactivate amygdala during sham; this may represent arousal-anxiety-driven failure of pain modulation. During baseline and sham, differences between patients and controls were found in sensory as well as affective-cognitive areas.