To evaluate the utility of monitoring the sound-filtering characteristics of the respiratory system in the assessment of acute lung injury (ALI), we injected a multifrequency broadband sound signal into the airway of five anesthetized, intubated pigs, while recording transmitted sound over the trachea and on the chest wall. Oleic acid injections effected a severe lung injury predominantly in the dependent lung regions, increasing venous admixture from 6 ± 1 to 54 ± 8% (P < 0.05) and reducing dynamic respiratory system compliance from 19 ± 0 to 12 ± 2 ml/cmH₂O (P < 0.05). A two- to fivefold increase in sound transfer function amplitude was seen in the dependent (P < 0.05) and lateral (P < 0.05) lung regions; no change occurred in the nondependent areas. High within-subject correlations were found between the changes in dependent lung sound transmission and venous admixture (r = 0.82 ± 0.07; range 0.74-0.90) and dynamic compliance (r = 0.87 ± 0.05; 0.80 to 0.93). Our results indicate that the acoustic changes associated with oleic acid-induced lung injury allow monitoring of its severity and distribution.