High-dose corticosteroid therapy has been advocated as adjunctive therapy in the adult respiratory distress syndrome (ARDS). We evaluated the effect of pharmacologic doses of corticosteroid (methylprednisolone and dexamethasone) on alveolo-capillary permeability in human septic ARDS by examining the change in appearance of intravenously administered iodine 131 (131I) human serum albumin (I-HSA) into broncho-alveolar secretions, before and after corticosteroid administration. Of 19 patients examined, in 14 (group 1) the clearance of I-HSA was reduced by corticosteroid (pre, .204 +/- .08 ml;/hr; post, .096 +/- .01 ml/hr; P less than .001), while in five (group 2) it was unaffected (pre, .23 +/- .02 ml/hr; post, .215 +/- .01 ml/hr; P=NS). Group 2 patients were more severely ill than group 1 patients in that their mean intrapulmonary shunt fractions and mean pulmonary artery pressures were higher. We conclude that high-dose corticosteroid therapy may reduce alveolo-capillary permeability in human septic ARDS if used early in the course of the illness.