The presence of myocardial depression is difficult to assess in most animal models of septic shock caused by hypovolemia. We studied endotoxemia in fluid-resuscitated conscious sheep. They underwent chronic instrumentation with pulmonary artery, arterial, and left atrial catheters. After 1 week of recovery, 1.5 micrograms/kg of endotoxin (LPS) was administered intravenously over a period of 30 min. One group of nine sheep stayed on baseline fluids (2 ml/kg/h of Ringer's lactate), while a second group (n = 6) was resuscitated with 7 ml/kg/h Ringer's lactate solution over the 24-h study period. Both groups were compared with controls. Eight hours after LPS, left ventricular stroke work index was depressed in both groups. In the group resuscitated with 7 ml/kg Ringer's lactate this depression associated with a normal left atrial pressure and a constant peripheral resistance indicated a shift in the Starling work curve downward and to the right evidencing myocardial depression.