We prospectively studied 18 patients with septic shock prior to and during volume infusion in order to evaluate their hemodynamic response to fluid repletion. Fluid challenge increased left heart filling pressure from 7.7 +/- 0.5 to 15.4 +/- 0.6 mm Hg (P less than .01). The increases in left ventricular filling were associated with significant increases in stroke volume index from 25.4 +/- 2.5 to 35.7 +/- 2.5 ml/min/M2 and cardiac index from 2.49 +/- 0.19 to 3.32 +/- 0.16 L/min/M2. However, at the end of fluid challenge, the patients exhibited depressed left ventricular performance as evidenced by a left ventricular stroke work index of 29.5 +/- 2.6 g X m/M2. Over the next 24 hours of maintenance fluid infusion, the left ventricular stroke work index increased to 36.8 +/- 4.2 g X m/M2 (not significant). These data suggest that volume infusion restores ventricular filling in patients with sepsis. Although fluid repletion increases stroke and cardiac output, depressed left ventricular performance appears to be an early finding in septic shock.