Ascites, a complicating feature of many diseases of the liver and peritoneum, commonly causes dyspnea. The mechanism of this symptom, however, is uncertain. In the present study, progressively increasing ascites was induced in anesthetized dogs and the hypothesis was initially tested that ascites increases the impedance on the diaphragm and so adversely affects the lung-expanding action of the muscle. Ascites produced a gradual increase in abdominal elastance and an expansion of the lower rib cage. Concomitantly, the caudal displacement of the diaphragm and the fall in airway opening pressure during isolated stimulation of the phrenic nerves decreased markedly; transdiaphragmatic pressure during phrenic stimulation also decreased. To assess the adaptation to ascites of the respiratory system overall, we subsequently measured the changes in lung volume, the arterial blood gases, and the electromyogram of the parasternal intercostal muscles while the animals were breathing spontaneously. Tidal volume and minute ventilation decreased progressively as ascites increased, leading to an increase in arterial Pco₂ and parasternal intercostal inspiratory activity. It is concluded that: (1) ascites, acting through both an increase in abdominal elastance and an expansion of the lower rib cage, impairs the lung-expanding action of the diaphragm; (2) this impairment elicites a compensatory increase in neural drive to the inspiratory muscles, but the compensation is not sufficient to maintain ventilation; and (3) dyspnea in this setting results in part from the dissociation between increased neural drive and decreased ventilation.