The expression of insulin-like growth factor-I (IGF-I), transforming growth factor-alpha (TGF-alpha) and p53 protein was examined in bronchial biopsy imprint smears of patients with primary lung cancer and benign lung disorders, by immunohistochemistry. Of the 44 malignant imprint smears, 26 (59%) were positively stained for IGF-I, 18 (41%) for TGF-alpha and 29 (66%) for p53 protein. In contrast, of the 36 benign imprint smears none was positively stained for IGF-I (p<0.001), whereas 7 were positively stained for TGF-alpha (p>0.05) and 3 for p53 protein (p<0.001). There was no correlation between the expression of the examined markers and the histological type of lung cancer. The most sensitive indicator of malignancy was p53 overexpression (65.9%), the most specific was IGF-I (100%) whereas both revealed 77.5% accuracy. The combination of IGF-I and p53 revealed 75% sensitivity, 91.6% specificity and 82.5% accuracy. When one marker was positive the relative possibility of lung cancer was 67.1%. This possibility increased to 77.7% when two markers were positive and to 100% when three markers were positive. These results suggest that the evaluation of IGF-I and p53 in imprint smears could be of value in diagnosis of lung cancer.