We have isolated DNA from 6 human lung tumor cell lines as well as several tumor cell lines carrying known oncogenes. These genomic DNAs were restriction-digested, electrophoresed, and probed with oligonucleotide probes to detect single-base mismatches in the Harvey, Kirsten, and N-ras proto-oncogenes at the codon 12 region and codon 61 region. Thus far, two previously uncharacterized lung tumor lines appear to carry mutations in the codon 12 region of Ki-ras, with the second allele being normal. A line previously shown to have a Ki- 12-ras mutation has been found to have lost the normal allele.