A study of serum p53 protein concentrations in lung cancer patients was conducted. The cohort consisted of 23 patients, 21 males, mean age 63.7 years, who underwent surgery for lung cancer in Helsinki, Finland in 1988. Twelve had definite or probable asbestos (1332214) exposure and 22 were smokers. The comparisons consisted of 23 patients who not been exposed to asbestos hospitalized for nonneoplastic diseases in New York City, matched by age and sex to the cohort (hospital comparisons), 58 healthy volunteers (34 females), mean age 44 years, (population comparisons), and four patients, two males, mean age 44 years, hospitalized for nonmalignant respiratory disease. Blood samples were collected and serum p53 concentrations were determined by an enzyme linked immunosorbent assay and Western blotting. Tumor tissue samples from 22 lung cancer patients were analyzed for p53 by an immunohistochemical technique. Tumor DNA was extracted and examined for mutations in the p53 gene by denaturing gradient gel electrophoresis mutational analysis. The mean serum p53 concentrations in the lung cancer patients, nonmalignant lung disease patients, hospital comparisons, and population comparisons were 0.55, 0.42, 0.32, and 0.31 nanograms per milliliter (ng/ml), respectively. None of the differences were statistically significant. Three lung cancer patients had serum p53 concentrations, 4.48, 3.29, and 2.08ng/ml that were more than two standard deviations higher than the comparisons. Tumor tissue samples from these patients contained elevated amounts of p53 and p53 gene mutations in their DNA. Increased tissue p53 concentrations were also found in tumors from six other patients and p53 gene mutations were found in tumor DNA from seven other patients. The authors conclude that elevated concentrations of serum p53 may occur in a proportion of lung cancer cases along with evidence of tumor tissue p53 alterations.