The clinical course of 33 patients with acute respiratory distress syndrome (ARDS) was monitored by noninvasive oxygen derived variables and compared to data obtained by invasive monitoring. A total of 350 data points were used to compare the physiologic shunt fraction (Qsp/Qt) with the ratio of arterial oxygen to inspired oxygen concentration (PaO2/FIO2), the alveolar-arterial oxygen pressure difference [P(A-a)O2], the respiratory index (RI)-[P(A-a)O2/PaO2], and the ratio of arterial oxygen to alveolar oxygen (a/A). The PaO2/FIO2 ratio, the RI and the aA ratio correlated well with Qsp/Qt (r = 0.87 to 0.94). The P(A-a)O2 correlated less well (r = 0.68). Changes in the cardiac index (CI) and the arteriovenous oxygen content difference C(a-v)O2 had only a minimal effect on the correlation of the oxygen derived variables with Qsp/Qt, although a higher correlation resulted when these extrapulmonary factors were within normal range. We conclude that a number of oxygen derived variables may accurately reflect the degree of Qsp/Qt. The PaO2/FIO2 ratio is the easiest of these variables to calculate, yet accurately predicts the degree of Qsp/Qt throughout a course of acute respiratory failure.