We describe an animal model of generalized sepsis, induced in the sheep by cecal perforation, which reproduces the high systemic flow and peripheral vasodilation seen in early human sepsis. Despite volume loading, animals demonstrate a fall in glomerular filtration rate, oliguria, low fractional sodium excretion, maintained urine osmolarity, and increased plasma renin activity. Histologically, kidneys show no consistent abnormality; overall the findings suggest volume contraction or hypoperfusion. This is contradicted, however, by maintained blood pressure and pulmonary capillary wedge pressure, increased cardiac output, and reduced peripheral resistance. Increased Fc lysozyme and low molecular weight proteinuria suggest tubular damage. These paradoxical observations are currently unexplained.