The relationship between delivery and uptake of O2 was evaluated in 20 patients with the adult respiratory distress syndrome (ARDS). Eleven patients were studied acutely, after progressive increments in positive end-expiratory pressure. The remaining 9 patients underwent serial determinations of gas exchange and O2 uptake during several days, because O2 delivery varied secondary to changes in clinical status or therapeutic interventions. In all but one patients, decreasing delivery of O2 led to similar decreases in uptake of O2. In general, changes in mixed-venous PO2 were variable and had no consistent relation to cardiac output or O2 delivery. In a contrasting group of 12 patients without ARDS, delivery and uptake of O2 were not related, and mixed-venous PO2 correlated well with cardiac output. We conclude that in patients with ARDS, there is a direct relationshipl between delivery of O2 and uptake of O2. Changes in mixed-venous PO2 may not reflect changes in O2 delivery, cardiac output, or the adequacy of tissue oxygenation. Failure to recognize this may lead to inappropriate evaluation of the clinical status of the patient or the efficacy of therapy.