Overexpression of epidermal growth factor receptor (EGF-R), K-ras gene mutations and c-myc gene amplification were studied in tumor and normal lung tissues from 100 patients with non-small cell lung cancer. The mean a standard deviation (SD) of the amount of EGF-R in the tumor (N=97) and the normal (N=82) tissues were 16.0 +/- 3.7 and 10.8 +/- 2.0 fmol/mg, respectively (P=0.015). Overexpression of the receptor was observed in 6 (24.0%) of 25 squamous cell carcinomas, 16 (23.2%) of 69 adenocarcinomas and 23 (23.7%) of a total of 97 tumors. K-ras mutations were observed in nine (9%) of 100 tumors. Of these, five (55.6%) mutations were in codon 12, one (11.1%) was in codon 22, and three (33.3%) were in codon 61. The patterns of the mutations were GC transversions in three (33.3%) tumors, GC transitions in two ( 22.2%) and AT transversions in four (44.4%) tumors. There was no association between EGF-R overexpression and K-ras mutation. c-myc amplification was studied in 23, but was not detected in any tumor (mean number of copies +/- SD = 1.28 +/- 0.24).