Decreased urinary output (Vu ml/min) after institution of PEEP is attributed to a variety of mechanisms including decreased cardiac output and renal blood flow (RBF), activation of neurohormonal reflexes, increased catecholamines, plasma renin activity (PRA), and antidiuretic hormone (ADH) release. To evaluate these factors, seven normovolemic patients (36 yr +/- 13 SD), free of preexisting lung, cardiac, or renal disease, requiring continuous mandatory ventilation for neurologic reasons were studied. The authors measured or calculated: total blood volume (TBV) (51Cr); right atrial, pulmonary arterial, pulmonary wedge, and systemic pressures, cardiac index (CI); renal plasma flow (RPF) (iodohippurate sodium 131I [131I PAH] clearance); glomerular filtration rate (GFR) (creatinine clearance), free water clearance (CH2O), osmolal clearance (Cosm), fractional excretion of sodium (FENa+) and potassium (FEK+); and plasma renin activity (PRA) (ng X ml-1 X h-1), plasma ADH (pg/ml; radioimmunoassay), epinephrine (E in pg/ml), and norepinephrine (NE in pg/ml) (double-isotope radioenzymatic assay). Two conditions were studied after 90-min steady state: 1) zero PEEP (ZEEP); and 2) 15 cmH2O PEEP. PEEP caused a significant decrease in CI (-21%; P less than 0.01) and RPF (-19%; P less than 0.05) without significant decrease in GFR. A significant decrease in Vu (-55%; P less than 0.05), FENa+ (-39%; P less than 0.05) and Cosm (-36%; P less than 0.25) occurred without modification in CH2O. Plasma ADH remained in the normal range and did not increase when PEEP was applied.(ABSTRACT TRUNCATED AT 250 WORDS)