Effects of endotoxemia on lung water, hemodynamics, and gas exchange were determined in ponies breathing a mixture of halothane and 100% O2. Escherichia coli endotoxin was infused IV at 20 micrograms/kg of body weight for 1 hour followed by 10 micrograms/kg/hr the subsequent 4 hours. By 0.25 hour, endotoxin increased mean pulmonary artery pressure and pulmonary vascular resistance; this was followed by a return to base-line values by 0.5 and 1 hour, respectively. A 2nd increase in pulmonary vascular resistance occurred by 5 hours of endotoxemia. During the last 2 hours of endotoxin infusion, cardiac index was significantly (P less than 0.05) decreased. Hematocrit was increased from 1 to 5 hours of endotoxemia, whereas, the plasma protein concentration was increased from 2 to 4 hours, indicating a loss of plasma volume. The PaO2 and PaCO2 were unchanged. After 5 hours of endotoxemia, lung extravascular thermal volume, postmortem bronchoalveolar lavage albumin content, and extravascular lung water/extravascular dry weight ratio of bloodless lungs were not increased, indicating no increase in alveolar-capillary permeability or pulmonary edema.