Genotyping of five CYP2D6 alleles (wt, A,B,D,E) has been performed in 218 lung cancer patients and 289 healthy controls. PCR-methods were used to determine the CYP2D6A and CYP2D6B alleles. Both patients and controls were of Caucasian Norwegian origin. In the lung cancer group all major histological types were represented. The frequency of the CYP2D6B allele which is associated with poor metabolizers (PM), was 0.235 in the lung cancer population and 0.200 in the control population. The frequencies of the CYP2D6A allele, another mutant allele associated with the PM-phenotype, were 0.007 and 0.013 in the lung cancer and control population respectively. RFLP analysis using the restriction enzyme Xba I to determine the D and E alleles, was also performed on 178 of the patients and on 118 of the controls. The frequency of the deletion variant CYP2D6D (13 kb) was 0.025 in the lung cancer group and 0.012 in the control group. None of these frequencies in the lung cancer patients were statistically significantly different from the frequencies of the control population. When combining the PCR-typing results (CYP2D6A, CYP2D6B) 20 individuals were found to carry two PM-associated alleles in the lung cancer group (n = 204) compared with only six among the controls (n = 117). This corresponds to a PM frequency of 9.8% in the lung cancer population compared with 5.1% in the control population which is, however, not significantly different from each other. These results are not in concordance with previous results which suggest that the EM-phenotype is a susceptibility marker for lung cancer.