The gene encoding the xenobiotic-metabolising microsomal enzyme, epoxide hydrolase (mEPHX), shows two common mutations, i.e. at exons 3 and 4. It is unknown how these genetic polymorphisms relate to risk of developing alcoholic liver disease (ALD) and/or hepatocellular carcinoma (HCC) in a Caucasian population. DNA samples extracted from the blood of 61 ALD patients and 203 healthy controls, and from archival liver tissue of 46 cases of HCC, were subjected to polymerase chain reaction amplification followed by digestion with EcoR V or Rsa I to demonstrate polymorphisms of exon 3 or 4, respectively. The distributions of the genotypes of exon 3 in the ALD and HCC patients, and exon 4 in the HCC patients did not differ significantly from those of the control group. However, compared with the control group, the ALD group contained a significantly greater number of individuals homozygous or heterozygous for the exon 4 mutation. This suggested association between possession of the exon 4 mutant mEPHX allele and increased risk of developing ALD may relate to known interactions between mEPHX and alcohol-metabolising enzyme systems, or to linkage disequilibrium between the mutation and other genetic risk factors for ALD.