A human lung tumor-associated antigen has been identified by Ouchterlony analysis in 86% of lung tumor extracts of all histologic types. It was not detected by this method in extracts of normal adult or fetal lung, 12/13 other tumors, normal tissues or in normal serum. The antigen was purified from the extract of an undifferentiated small cell lung carcinoma by DEAE-cellulose. Sephadex G-200, and antibody affinity chromatography. The purified antigen exhibited size and charge heterogeneity, yet all isolated forms produced precipitin lines of identity with each other, as well as with an extract of an unrelated squamous cell carcinoma of the lung. The major form had a Mr of 150 000 by gel filtration and 81 700 by detergent gel electrophoresis. By radioimmunoassay, elevated levels of antigen were detected in 0/15 normal sera, 7/13 stage I and 12/15 stage III lung cancer sera. The urine of a different patient with a small cell lung carcinoma contained a related antigenic activity, but the major component was 30 000-50 000 daltons. The antigen has also been detected in extracts of a continuous cell line from a large cell carcinoma of the lung (ChaGo). The antigen is being evaluated for its usefulness as a lung tumor marker.