Recent reports have shown that oxygen delivery (Do2) and oxygen uptake (Vo2) could be related to outcome of critically ill patients. In this study, we examined measurements of cardiac output, oxygen-derived variables, and blood lactate levels in 48 patients with documented septic shock. There were 27 survivors and 21 nonsurvivors from the shock episode. For all 174 observations, there was a significant linear relationship between Vo2 and Do2 (Vo2 = 79 + 0.17 x Do2, r = 0.64, p less than 0.001). There were no significant differences in Do2 between survivors and nonsurvivors at the onset of septic shock (mean +/- SD, 540 +/- 219 vs 484 +/- 222 ml/min.m2, NS) or in the final phase of septic shock (506 +/- 163 vs 443 +/- 187 ml/min.m2, NS). Also, no significant differences were found in Vo2 and oxygen extraction between survivors and nonsurvivors. However, survivors had significantly lower blood lactate levels both initially (5.1 +/- 2.7 vs 8.2 +/- 5.4 mmol/L, p less than 0.05) and in the final phase of septic shock (2.6 +/- 1.9 vs 7.7 +/- 5.6 mmol/L, p less than 0.001). Only the survivors had a significant decrease in blood lactate levels during the course of septic shock (p less than 0.001). We conclude that the oxygen-derived variables, Do2 and Vo2, cannot be used as prognostic indicators in human septic shock. In contrast, blood lactate levels are closely related to ultimate survival from septic shock. Furthermore, decreases in blood lactate levels during the course of septic shock could indicate a favorable outcome. Therefore, blood lactate levels can serve as a reliable clinical guide to therapy.