Matrix metalloproteinase-9 (MMP-9) plays an essential role for metastasis. The purpose of this study is to investigate the significance of active MMP-9 quantified in serum of patients with non-small cell lung cancer. Immunohistochemical staining of the primary tumors was also performed to analyze how much the secretion of MMP-9 from cancer cells influences the concentration of MMP-9 in serum. The preoperative sera of 39 patients with NSCLC, who underwent an operation at our institution from 1996 to 1999, were taken before the operation. Forty-three samples of sera were drawn postoperatively. Of these 43 samples, 16 sera were taken from patients who suffered with recurrence, 27 sera were taken from patients who did not suffer with recurrence. The serum level of active MMP-9 of preoperative state was 24.3 +/- 21.2 ng/ml, which was higher than that of control was 14.6 +/- 18.8 ng/ml, but no significance was recognized statistically between them (P = 0.0666). The immunoreactivity of MMP-9 was not correlated statistically with serum level of total MMP-9 and active MMP-9. The activity ratio of non-recurrent group was also a lower level than that of recurrent group (P = 0.0082). In conclusion, our results suggest that the concentration of serum active MMP-9 has a possibility of being an available marker to detect a recurrent disease. Our findings strongly suggest that measuring the activity ratio of serum MMP-9 appears to be a potentially useful tumor maker.