The purpose of this study was to investigate the effect of i.v. infusion of atrial natriuretic peptide (ANP) on hemodynamics, pulmonary gas exchange, and urine volume during mechanical ventilation with positive end-expiratory pressure (PEEP) in patients with acute lung injury. Prospective, randomized, comparable study. ICU of a university hospital. Forty patients with moderate acute lung injury (lung injury score > or = 2.0) who required mechanical ventilation with PEEP were studied. The patients were randomly divided into two groups: ANP group (n=20) and control group (n=20). The ANP group received genetic recombination alpha-human ANP (carperitide) at the rate of 0.1 microg/kg/min for 24 h. The control group did not receive ANP. Hemodynamic and blood gas parameters, and urine volume were measured at baseline, 3 h, and 24 h after initiating the ANP infusion. Plasma ANP concentrations markedly (p<0.01) increased from 112.0+/-27.0 to 1,868.3+/-385.3 pg/mL after 24 h in the ANP group, whereas they remained unchanged in the control group. In the ANP group, hemodynamic parameters did not change, but PaO2/FIO2 (fraction of inspired oxygen) and thoracic compliance significantly (p<0.01) increased at 24 h after initiating the ANP infusion, associated with significant (p<0.01) decreases in lung injury score and shunt. Urine volume significantly (p<0.01) increased during 0 to 3 h after initiating the ANP infusion. In the control group, hemodynamics, pulmonary gas exchange, and urine volume did not significantly change during the study period. There were significant differences in PaO2/FIO2 (24 h), thoracic compliance (24 h), lung injury score (24 h), and urine volume (3 h) between the two groups. The results suggest that ANP infusion induces diuresis and improves pulmonary gas exchange in patients with acute lung injury during mechanical ventilation with PEEP.