Auto-antibodies against L-myc oncogene products (L-Myc) in sera from lung cancer patients were examined using bacterially synthesized glutathione S-transferase (GST) L-Myc fusion proteins and Western blot analysis. The detection rate of anti-L-Myc antibodies in sera from lung cancer patients was 10%, while that in sera obtained from normal volunteers was 0%. Five patients with non-small-cell lung cancers (2 adenocarcinomas, 2 squamous-cell carcinomas and I large-cell carcinoma) were included in the group with anti-L-Myc antibodies. These auto-antibodies belonged to the IgG class and recognized the carboxy terminus of L-Myc. Circulating L-Myc was not detected in sera from patients with anti-L-Myc antibodies. Differences in age, sex, performance status, histology, stage, smoking history and prior treatment were not significantly different between anti-L-Myc antibody-positive and antibody-negative patients. Anti-nuclear antibodies were detected in 40% of lung cancer patients and 57% of those with anti-L-Myc antibodies. Our data suggest that detection of anti-L-Myc antibodies may be helpful in the diagnosis and evaluation of the host-immune response to L-Myc in a subset of lung cancer patients.