To evaluate the diagnostic value of the serum cytokeratin 19 fragment (CYFRA 21-1) in bronchogenic carcinoma, we investigated the sera of 138 patients (58 with benign pulmonary disease and 80 with non-small cell lung cancer (NSCLC)) using immunoradiometric assay. The mean (SD) value of serum CYFRA 21-1 in NSCLC (13.26 (16.54)) was significantly higher than in benign lung diseases (1.74 (1.55)) (p < 0.0001). Sensitivity for CYFRA 21-1 (using 3.5 ng/ml, a cut-off value corresponding to a 95% specificity for benign pulmonary disease) in NSCL was 62%. Positive CYFRA 21-1 levels were significantly higher in 75% of patients with squamous cell carcinoma (n = 36) than in 53% with other NSCLC (n = 44) (p < 0.05). CYFRA 21-1 levels were significantly different between squamous cell carcinoma (17.28 (19.94)) and the other NSCLC (9.96 (12.44)) (P < 0.05). Elevated CYFRA 21-1 levels in patients with stage III and IV disease (n = 64, 18.19 (26.51)) were significantly higher than in stage I and II (n = 16, 4.41 (5.76)) (p < 0.02). The positive rate of CYFRA 21-1 in tumor stage I and II was only 37%. Our results indicate that CYFRA 21-1 may be a useful tumor marker in NSCLC, especially in squamous cell carcinoma. However, CYFRA 21-1 cannot be used for the diagnosis of early stage disease of NSCLC. CYFRA 21-1 may also contribute to the monitoring of NSCLC.