The authors examined the effects of high ketone body and glucose concentrations on endothelial cell (EC) function in perfused rabbit lungs. beta-Hydroxybutyrate (beta OHB), at 5 mM, decreased endothelial angiotensin-converting enzyme (eACE) activity, whereas 25 mM glucose (HG), 1 mM beta OHB, or 10 mM acetoacetate (AcAc) did not. Dry to wet weight ratios were also reduced in lungs perfused with 5 mM beta OHB, but not with AcAc. beta OHB, at 5 mM, caused massive hemorrhage and interstitial and alveolar neutrophil infiltration; AcAc only produced engorgement of septal capillaries. Thus, pulmonary EC dysfunction occurs in rabbit lungs acutely perfused with beta OHB, but not with AcAc or glucose.