The increase in opioidergic tone by the central administration of morphine, which binds to the mu opioid receptor, is associated with pruritus. Pruritus is a symptom of cholestasis, which appears to result, in part, from increased opioidergic tone; a central mechanism has been proposed. The single nucleotide polymorphism Al18G in exon 1 of the opioid receptor mu 1 (OPRM1) gene, which codes for the mu opioid receptor, has been associated with alterations in functions mediated by the endogenous opioid system. In this study we found A118G in heterozygosity in 29% of the DNA samples from patients with primary biliary cirrhosis from the USA and from Italy with and without pruritus. A118G was 1.5 times more frequent in the samples from patients without pruritus from the USA than in the rest of the samples. The possibility of protection from pruritus associated with A118G supports the study of genetic polymorphisms of the OPRM1 gene in patients with cholestasis.