Mice lacking matrix metalloproteinase-3 (MMP-3; stromelysin-1) demonstrated significantly less injury than their normal counterparts following the formation of IgG-containing immune complexes in the alveolar wall or in the wall of the peritoneum. Likewise, mice lacking MMP-3 demonstrated less lung injury following intra-tracheal instillation of the chemotactic cytokine macrophage inhibitory protein-2 (MIP-2) than did mice with MMP-3. There was a relationship between tissue injury (evidenced histologically) and accumulation of anti-laminin 111 immunoreactive material in the bronchoalveolar lavage (BAL) or peritoneal lavage (PL) fluid. There was also a relationship between tissue injury and influx of neutrophils into the BAL or PL fluid. Taken together, these data demonstrate an important role for MMP-3 in acute inflammatory tissue injury.