Although the c-jun oncogene is an integral part of the AP-1 transcriptional complex implicated in the process of tumor promotion, its role in the pathogenesis of human tumors is unknown. We analyzed the expression and function of cJun in 110 non-small cell lung cancer (NSCLC) primary and metastatic tumors, histologically atypical areas from the surrounding lung, and 10 NSCLC cell lines to examine the role of cJun in lung carcinogenesis. cJun was expressed in primary and metastatic lung tumors in 31% of cases, with no association with survival. Whereas normal conducting airway and alveolar epithelia in general did not express cJun by immunohistochemistry, histologically atypical areas were frequently positive for cJun, regardless of the status of the corresponding tumor. Multiple members of the jun and/os gene families were frequently expressed at the mRNA level in vitro, with detectable functional activity (as defined by AP-1- specific DNA binding and/or transactivation of an AP-1-driven reporter construct) present in all 10 NSCLC cell lines examined. Although tumor- promoting phorbol esters had little effect on c-jun expression, serum stimulation generally resulted in significant c-jun induction in NSCLC cell lines. These data show that cJun expression is altered early during human lung carcinogenesis and that cJun may function as a mediator of growth factor signals in NSCLC.