We examined by immunoblotting antibodies that bind to p16(INK4A) tumor suppressor gene products in the sera of patients with lung cancer. Sera from 15 to 102 patients, including 6 with adenocarcinoma, 3 with squamous cell carcinoma, 2 with large cell carcinoma and 4 with small cell carcinoma, reacted with a glutathione-S-transferase (GST) fusion protein containing whole human anti-p16(INK4A), produced by Escherichia coli. However, sera from 30 normal volunteers did not react with the GST-p16(INK4A) fusion protein. The background such as age, gender, performance status, histology, stage, smoking history, and prior treatment was not significantly different between the patients with and without anti-GST-p16(INK4A) antibodies. Circulating p16(INK4A) tumor suppressor products were not detected in any individuals with lung cancer or in the normal controls.