We studied non-small cell lung cancers (NSCLC) from 60 patients for abnormalities in the c-erbB-2 gene. Eleven human lung cancer cell lines, including four derived from small cell lung cancer (SCLC) and seven derived from NSCLC were also examined for altered c-erbB-2 gene expression. Southern blot analysis of paired tumor and normal lung samples demonstrated that amplification of the c-erbB-2 gene is rare in NSCLC (2/60) and not restricted to adenocarcinomas. One patient showed an EcoRI restriction fragment length polymorphism for the c-erbB-2 locus. Four of four SCLC cell lines demonstrated minimal or nondetectable expression of c-erbB-2 mRNA compared to high levels of expression by seven of seven NSCLC lines. The highest expression levels were seen in four of four adenocarcinomas. We conclude that c-erbB-2 expression is different in SCLC compared to NSCLC and high expression of c-erbB-2 is consistently present in lung adenocarcinomas.