A functional promoter polymorphism (-116C/G) of the X-box binding protein 1 gene (XBP1) gene was reported to be associated with schizophrenia in Asian subjects. In a replication attempt, three European case-control samples comprising 2,182 German, Polish, and Swedish subjects, were genotyped for the XBP1 -116C/G polymorphism. Allele and genotype frequencies were compared between schizophrenic patients and control subjects. There were no significant case-control differences in any of the three samples, although in a meta-analysis with previous results comprising 3,612 subjects there was a borderline association between the -116G-containing genotypes and schizophrenia. We conclude that the functional XBP1 gene polymorphism is not of major importance to schizophrenia in the European populations investigated. It cannot be excluded, however, that the XBP1 polymorphism is involved in schizophrenia in other populations or adds minor susceptibility to the disorder.