The virulence of Pseudomonas aeruginosa is partly controlled by the las quorum-sensing system. A rat model of acute pneumonia was used to investigate the pathophysiological impact of this system by comparing the virulence of the wild-type virulent laboratory strain PAO1 with that of its lasR-deleted mutant PAOR. In comparison with PAO1, PAOR was avirulent after an instillation of 106 cfu (mortality rates, 72 versus 0%, respectively; p < 0.0001). A ten-fold higher inoculum slightly increased the mortality rate induced by PAOR (25%), which remained lower than that induced by PAO1 (75%, p = 0.0001). In addition, with both inocula lung and bronchoalveolar lavage bacterial counts were significantly lower in rats infected with PAOR than with PAO1 (p </= 0.01). Histopathological analysis showed that PAO1 induced a drastic vascular congestion and neutrophil infiltration of the lungs, whereas lung injury in rats infected with PAOR was mild with predominantly macrophage infiltration. This study adds evidence that the quorum-sensing system has an important role in the pathophysiology of P. aeruginosa pulmonary infection.