Recently CYFRA 21-1, a new tumour marker measuring a fragment of cytokeratin 19, was introduced and proved to be suitable for the follow-up care and monitoring of the therapy of non-small cell lung carcinomas, especially squamous cell carcinomas of the lung. Besides CYFRA 21-1, there are two other tumour markers available, called tissue polypeptide antigen (TPA) and tissue polypeptide specific antigen (TPS), which also measure different cytokeratins in serum. In a retrospective study we investigated the clinical significance of these 3 cytokeratin markers in lung cancer compared with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). We investigated the sera of 50 healthy persons, 273 patients with various benign diseases and 218 patients with histologically proven lung cancer. In a first step the specificity versus benign diseases of the lung was established for all the markers, and was fixed at 95%. Then the single and combined sensitivities were calculated. CYFRA 21-1 proved to possess the highest sensitivity in lung cancer in general (61%), in non-small cell lung carcinomas (64%), in squamous cell carcinomas (79%), in adenocarcinomas (54%) and in large cell carcinomas (65%). In small cell lung carcinomas, neuron-specific enolase proved again to be the marker of first choice (55%). Combined determinations proved clearly increased sensitivity only for large cell carcinomas (CYFRA 21-1 + TPA: 77%) and for small cell lung carcinomas (CYFRA 21-1 + NSE: 62%).(ABSTRACT TRUNCATED AT 250 WORDS)