Loss of function of the p53 tumor supressor gene is involved in nearly all human cancer. Recently a cellular oncogene product, mdm2, has been shown to bind to p53 and eliminate its ability to function as a transcription factor. mdm2 and p53 immunohistochemical protein expression was studied in tumor tissues, preneoplastic lesions, and normal bronchial mucosa. The specimens were obtained during diagnostic bronchoscopy from 53 patients with lung cancer. In the tumor specimens, p53 nuclear staining was detected in 26 (49%) cases, mdm2 in 11 (20.7%), and simultaneous expression of both proteins in 6 (11.3%) cases. Thirty-five sections with preneoplastic lesions were found in 21 patients. p53 nuclear staining was found in 11 of 35 and mdm2 in 6 of 35 sections. In normal cells, mdm2 positive staining was found in 18 and p53 in 12 specimens. Simultaneous p53 and mdm2 expression was found in 4 specimens. Our results indicate that p53 expression is more frequent than mdm2 expression in lung cancer tissues. Alterations in these proteins are early events and may represent alternative pathways in carcinogenesis.