This study was undertaken to evaluate the circulating urokinase plasminogen activator (uPA), and its soluble receptor (suPAR) in patients with either small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC). Thirty-one male and female patients with stage III or IV NSCLC and 17 with stage III or IV SCLC were compared to 138 age-matched non-smoking controls of both sexes. Before any treatment was undertaken, serum was obtained and evaluated for its content of uPA and suPAR with enzyme-linked immunosorbent assay. The results indicated a wide variation in serum uPA content that was not significant, while extremely significant increases in suPAR were found. The natural physiologic relationship between uPA and its receptor was lost in both SCLC and NSCLC, which could indicate abnormal alterations of uPA suPAR, suggesting these factors aid in the process of invasion and metastasis of lung cancer.