In anesthetized mongrel dogs we investigated the effects of hypovolemia and beta-adrenergic stimulation on the decrease in force generation by the diaphragm [transdiaphragmatic pressure (Pdi)] during electrical stimulation of the phrenic nerves for 1 h. In seven normovolemic dogs with arterial pressure (Pa) of approximately 125 Torr, Pdi fell approximately 48% from an initial value of 35 +/- 4.8 Torr. In dogs made moderately hypovolemic, Pdi was actually higher than with normovolemia (P less than 0.01). In dogs made severely hypovolemic, Pa approximately 50 Torr, Pdi at the start of pacing was less than with normovolemia (25 +/- 1.5 Torr) and remained so during phrenic nerve stimulation. When beta-adrenergic blockade with propranolol was added to moderate hypovolemia, the values of Pdi became similar to those of severe hypovolemia. Analysis of the relative contributions of gastric pressure and pleural pressure revealed that the factor responsible for maintaining Pdi with moderate hypovolemia was pleural pressure. Changes in thoracic gas volume and chest wall configuration did not explain the changes we saw in diaphragm function. Analysis of the relationship between rib cage motion and pleural pressure confirmed our finding of the greater pleural pressure generation with sympathetic stimulation that accompanies hypovolemia. These studies demonstrated that 1) severe hypovolemia impaired diaphragm function, 2) diaphragm function was maintained with moderate hypovolemia by beta-adrenergic stimulation, and 3) with hypovolemia-associated sympathetic stimulation there was an increase in force generation by the intercostal muscles.