Reduced renal blood flow (RBF) is considered central to the pathogenesis of septic acute renal failure (ARF). However, no controlled experimental studies have continuously assessed RBF during the development of severe septic ARF. We conducted a sequential animal study in seven female Merino sheep. Flow probes were implanted around the pulmonary and left renal arteries. Two weeks later, systemic hemodynamics and RBF were monitored continuously during a 48-h control period and, after a week, during a 48-h period of hyperdynamic sepsis induced by continuous Escherichia coli infusion. Infusion of E. coli induced hyperdynamic sepsis with significantly increased cardiac output (3.8±0.4 vs 9.8±1.1 l/min; P<0.05), decreased mean arterial pressure (89.2±3.2 vs 64.3±5.3 mm Hg; P<0.05), and increased total peripheral conductance (42.8±3.5 in controls vs 153.7±24.7 ml/min/mm Hg in septic animals; P<0.05). Hyperdynamic sepsis was associated with marked renal vasodilatation (renal conductance: 3.0±0.7 vs 11.4±3.4 ml/min/mm Hg; P<0.05) and a marked increase in RBF (262.3±47.7 vs 757.4±250.1 ml/min; P<0.05). Serum creatinine increased over 48 h (73±18 vs 305± μmol/l; P<0.05) whereas creatinine clearance decreased (95.5±25.9 vs 20.1±19.3 ml/min; P<0.05). After 24 h, urine output decreased from 1.4 to 0.3 ml/kg/h (P<0.05). Infusion of E. coli induced hyperdynamic sepsis and ARF. Septic ARF in this setting was associated with a marked increase in RBF and with renal vasodilatation.