Fifty-four patients with systemic sepsis and signs of circulatory shock were prospectively investigated immediately before and after 1 of 3 therapeutic interventions chosen to increase systemic oxygen delivery (DO2): colloidal fluid loading (Group I, n = 20), blood transfusion (Group II, n = 17), or catecholamine infusion (dopamine or dobutamine, Group III, n = 17). Patients in Groups I and II with normal blood lactate concentrations (less than 2.2 mmol/L) exhibited no significant increases in systemic oxygen consumption (VO2) in response to the increases in DO2. However, significant increases in VO2 were noted in patients in Groups I and II with elevated lactate concentrations (greater than 2.2 mmol/L). In contrast to patients in Groups I and II, patients in Group III with and without lactic acidosis exhibited significant increases in VO2 after catecholamine administration. Lactic acidosis, a clinical marker of anaerobic metabolism or oxygen debt, appears to predict increases in VO2 in response to increases in DO2 in septic patients receiving fluid and catecholamines increase VO2 without regard for the presence or absence of anaerobic metabolism. The results of this clinical trial therefore suggest that catecholamines may exert a direct effect on oxidative metabolism.