Proteases contribute to tumor invasion and metastasis via their potential to degrade basement membranes and extracellular matrix. Our aim was to compare the level of several proteases: urokinase-type plasminogen activator (u-PA), matrix metalloproteinase 2 (MMP-2; 72-kDa type IV collagenase, also known as gelatinase A), MMP-11 [also known as stromelysin 3 (STR3)], and cathepsins B and L in resected non-small cell lung cancer. Between June 1996 and March 1998, samples of lung tumor tissues were taken from 119 surgically treated patients. Thirty out of the 119 tumor samples were matched with corresponding adjacent normal tissue. u-PA was measured by a commercially available immunoluminometric assay. Metalloproteinases and cathepsins have been evaluated at the RNA level by Northern blot and quantified with a PhosphorImager. Expression of these proteases was compared to the following clinicopathological parameters: pathological diagnosis, tumor size, exposure to asbestos, radiotherapy, neo-adjuvant chemotherapy, tumor-node-metastasis stage, lymph node involvement, presence of metastasis. u-PA, MMP-2, MMP-11/STR3, and cathepsin B were significantly increased in tumor (the tumor:normal ratio was on average increased by 5.4-, 2.2-, 83.5-, and 2.2-fold, respectively). The tumor:normal ratio of MMP-11/ STR3 was found to be significantly linked to the lymph node involvement (P < 0.05). Our results suggest that several proteases are involved in the invasive potential of non-small cell lung cancer and that the quantification of MMP-11/ STR3 could represent an useful prognostic marker.