Anti-LKM-1 autoantibodies are directed mostly at cytochrome P450 2D6 (CYP2D6) autoantigen, whose activity ranges from "complete deficiency" to "extensive metabolism" due to genetic polymorphism. We aimed to find any relevance of CYP2D6 alleles to the presence/absence of anti-LKM-1 in Japanese patients with chronic hepatitis C. The frequency of an extensive metabolizer-type allele (CYP2D6*1) in anti-LKM-1-positive patients was higher than that in anti-LKM-1-negative patients (0.800 vs 0.431; P = 0.0035), while the CYP2D6*10 allele with moderately reduced activity was less frequent in the former than the latter (0.050 vs 0.389; P = 0.0069). Moreover, the rate of homozygosity for CYP2D6*1 showed a striking difference between the two groups (70% vs 19%; P = 0.0021). These findings suggest that a genetic predisposition to produce the enzyme CYP2D6 of extensive metabolizer-type is associated with the induction of anti-LKM-1 in chronic hepatitis C patients.