Abstract:  Schizophrenia is a complex disease caused by interactions among multiple genes. Reports of one of its susceptibility genes, ethyltracatechol-O-mnsferase (COMT) have been conflicting. In the present study on paranoid schizophrenia, we have performed a multilocus association study to analyze the interactions among 4 genes that are involved in dopamine metabolism. Result supports the hypothesis that COMT-136-BclI regulates Val^108/158Met. When the genotype of the former is CC, Met (A) is the genotype of susceptibility allele Val^108/158Met; and when the genotype of the former is GG, Val (G) is the genotype of susceptibility allele Val^108/158Met. This new hypothesis may explain the conflicting results about Val^108/158Met (COMT) obtained by single-locus analyses. It also illustrates that multilocus analysis is necessary for the research of complex diseases.