Matrix metalloproteinases (MMPs) are associated with tissue destruction and remodeling in various inflammatory and malignant diseases. In the preterm infant development of lung injury is characterized by inflammation and subsequent fibrosis. MMPs have not been previously identified in preterm lung. In tracheal aspirate samples (N=48) taken during the first postnatal week from 9 intubated preterm infants (gest. age 24-28 wks, mean 26.1 wk) MMPs, endogenous tissue-inhibitors of MMP (TIMPs) and proMMP-activating serine protease (trypsins) were analyzed by gelatin-zymograms and immunoblotting using specific antibodies. The samples were found to contain both collagenolytic, gelatinolytic, and serine protease activities. Immunological characterization revealed that the major collagenase was collagenase-2(neutrophil collagenase, ie MMP-8), which dominated over its cousins fibroblast-type MMP-1 and collagenase-3 (MMP-13). The major gelatinase was gelatinase-A (MMP-2) that dominated over gelatinase-B (MMP-9). Both native and fragmented forms of TIMPs were present, and MMP-activating serin protease trypsin was also found in the samples. We conclude that MMP-activating cascade is present postnatally in the preterm lung, and may participate in the pathogenesis of chronic lung injury.