We studied the prevalence of point mutations in ras oncogenes (K-ras and N-ras) in DNA from white blood cells and tumor tissue from 36 untreated patients with non-small-cell lung cancer, all of whom were smokers or ex-smokers. We observed somatic K-ras mutations in one-third of the lung carcinomas studied but no N-ras mutation. K-ras codon 12 mutations were found more frequently in adenocarcinomas than in the other histopathological subtypes studied. More than 60% (10/16) of the lung adenocarcinomas had a codon 12 mutation, most of which were G to T transversions. No mutations was found in white blood cell DNA. Two polymerase chain reaction screening methods, oligonucleotide hybridization and denaturing gradient gel electrophoresis (DGGE), were used to detect the mutations. The oligonucleotide method appears to be more sensitive than DGGE, but DGGE proved to be a reliable nonradioactive method for rapid screening of point mutations in genes relevant to carcinogenesis.