Background & Aims: Symptoms in functional dyspepsia have been related to impaired accommodation and hypersensitivity of the proximal stomach. We hypothesized that identification of putative antral dysfunctions provides a more comprehensive pathophysiological interpretation. Methods: In 30 patients with functional dyspepsia and 22 healthy subjects, 2 consecutive studies were performed. In study I, with the subjects in the upright position, the proximal and distal stomach were selectively distended by bags containing air and water, respectively, while perception and fundic relaxation in response to antral distention were measured. In study II, by using air-filled bags connected to a tensostat, the proximal and the distal stomach were selectively distended by positioning the subjects on the right and left lateral decubitus, respectively, while perception, compliance, and the responses to intestinal nutrient infusion were measured. Results: Patients with dyspepsia showed hypersensitivity of both the proximal stomach (discomfort at 30 ± 3 g vs. 62 ± 2 g in controls; P < 0.05) and the antrum (discomfort at 31 ± 2 g vs. 53 ± 4 g in controls; P < 0.05). Fundic and antral fasting tone was normal, but reflex fundic relaxation induced either by antral distention (3 ± 16 mL at 80 mL of distention vs. 38 ± 10 mL in controls; P < 0.05) or by intestinal nutrients (35 ± 7 mL vs. 107 ± 8 mL in controls; P < 0.05) was markedly impaired. Conclusions: Antral and fundic dysfunctions interact to produce the symptoms of functional dyspepsia, and impaired control of fundic accommodation may lead to overload of a hypersensitive antrum.