Previous studies have demonstrated that polymorphisms in the putative promoter region of the human serotonin receptor 1B (HTR1B) gene affect gene expression [H.F. Sun, Y.T. Chang, C.S. Fann, C.J. Chang, Y.H. Chen, Y.P. Hsu, W.Y. Yu, A.T. Cheng, Association study of novel human serotonin 5-HT(1B) polymorphisms with alcohol dependence in Taiwanese Han, Biol. Psychiatry 51 (2002) 896-901; J. Duan, A.R. Sanders, J.E. Molen, L. Martinolich, B.J. Mowry, D.F. Levinson, R.R. Crowe, J.M. Silverman, P.V. Gejman, Polymorphisms in the 5'-untranslated region of the human serotonin receptor 1B (HTR1B) gene affect gene expression, Mol. Psychiatry 8 (2003) 901-910]. And the silent mutation G861C allele has been reported to be associated with several psychiatric disorders. Thus, we performed a case-control association study (456 cases and 557 controls) of the five variants in HTR1B gene (T-261G, -182INS/DEL-181, A-161T, C129T and G861C) with schizophrenia. The results showed that neither the allelic distribution nor the major haplotype distribution (except for a rare haplotype) of five SNPs in patients was significantly different from that in controls. A further family-based association study (229 family trios) of G861C allele suggested that HTR1B was not a susceptible gene with schizophrenia in our sample. In conclusion, these data do not support the idea that HTR1B gene plays a major role in the etiopathogenesis of schizophrenia in Chinese Han population.