CYFRA 21-1, CEA, CA 125, SCC and NSE serum levels were determined in 50 healthy subjects and in 189 patients with primary lung cancer (101 with locoregional disease, 68 with recurrence and 20 patients with no evidence of residual disease (NED). Abnormal CYFRA 21-1 serum levels were found in 53.6% (90/168) of the patients with active cancer. Neither healthy subjects nor NED patients had abnormal serum levels. CYFR alpha 21-1 serum concentrations were significantly higher in patients with active cancer than in healthy subjects or in NED patients (p < 0.0001). CYFRA 21-1 sensitivity was related to tumor histology with abnormal levels in 64.7% of patients with NSCLC and in 30% of patients with SCLC (P < 0.0001). In NSCLC, serum CYFRA 21-1 concentrations were also related to histological type, the highest values being found in squamous cell carcinomas and LCLC and the lowest in adenocarcinomas (p < 0.04). There was also a clear relationship between CYFRA 21-1 and tumor extension, with significantly higher values in patients with metastases than in those without metastases (p < 0.0001). Abnormal CEA values were found in 49.1%, CA 125 in 39%, SCC in 27.8% and NSE in 21.3% of the patients with active cancer.(ABSTRACT TRUNCATED AT 250 WORDS)