BACKGROUND Clinical interest in xenon has been rekindled recently by new recycling systems that have decreased its relative cost. The cardiovascular effects of xenon were examined in isoflurane-anesthetized dogs before and after the development of rapid left ventricular (LV) pacing-induced cardiomyopathy. METHODS Dogs (n = 10) were chronically instrumented to measure aortic and LV pressure, LV subendocardial segment length, and aortic blood flow. Hemodynamics were recorded, and indices of LV systolic and diastolic function and afterload were determined in the conscious state and during 1.5 minimum alveolar concentration isoflurane anesthesia alone and combined with 0.25, 0.42, and 0.55 minimum alveolar concentration xenon in dogs with and without cardiomyopathy. RESULTS Administration of xenon to healthy dogs anesthetized with isoflurane decreased heart rate and increased the time constant (tau) of isovolumic relaxation but did not alter arterial and LV pressures, preload recruitable stroke work slope, and indices of LV afterload. Chronic rapid LV pacing increased the baseline heart rate and LV end-diastolic pressure, decreased arterial and LV systolic pressures, and produced LV systolic and diastolic dysfunction. Administration of xenon to isoflurane-anesthetized, cardiomyopathic dogs did not alter heart rate, arterial and LV pressures, myocardial contractility, and indices of early LV filling and regional chamber stiffness. More pronounced increases in tau were accompanied by increases in total arterial resistance during administration of xenon to isoflurane-anesthetized cardiomyopathic compared with healthy dogs. CONCLUSIONS The results indicate that xenon produces minimal cardiovascular actions in the presence of isoflurane in dogs with and without experimental dilated cardiomyopathy.