Croup and epiglottitis, which cause greater than normal negative inspiratory intrathoracic pressure (NIIP), have been associated with pulmonary edema. To examine the effects of increased NIIP per se on blood gases, hemodynamics, and lung water content, we carried out 2 types of experiments in 18 anesthetized dogs. Short-term, low-pressure experiments (6 control dogs and 6 dogs that generated intratracheal pressures of -12 cm H2O during inspiration for 3 h) and long-term, high-pressure experiments (6 dogs that generated -20 cm H2O during inspiration for 6 h). In the short-term, low-pressure experiments, animals made to generate negative inspiratory pressure differed from control dogs by demonstrating decreased pleural pressure (p less than 0.01), increased arterial PCO2 (p less than 0.05), and decreased minute volume (p less than 0.05); no differences occurred in hemodynamic data (pulmonary arterial, left atrial, and aortic pressures and cardiac index) and in extravascular lung water (indicator dilution and gravimetric analyses). Similarly, in the long-term, high-pressure dogs, arterial PCO2 increased (p less than 0.05) and lung water was normal by gravimetric analysis. We conclude that both 3 and 6 h of increased NIIP cause CO2 retention but have minimal effects on hemodynamics and lung fluid exchange.