An increasing amount of evidence suggests that the pathophysiology of schizophrenia is associated with activation of the immune system. Four studies have established an association of -308G/A polymorphism of tumor necrosis factor alpha (TNF-alpha), a cytokine involved in inflammatory processes, with schizophrenia [Mol. Psychiatry 6 (2001) 79; Mol. Psychiatry 8 (2003) 718; Schizophr. Res. 65 (2003) 19; Biol. Psychiatry 54 (2003) 1205]. In the present study, however, no significant positive association has been found between any individual SNP or haplotype constituted of the five promoter polymorphisms (-1031T/C, -863C/A, -857C/T, -308G/A and -238G/A) in the human TNF-alpha gene and schizophrenia (314 Chinese Han schizophrenic patients and 340 healthy control). A meta-analysis we did in this work, which is based on previous nine studies plus our own unpublished data including a total of 2399 schizophrenic patients (sporadic cases 2099, familial cases >505) and more than 3261 controls, failed to show significant difference of -308G/A distribution between patients and controls in both the whole sample and the pooled Asian sample. By contraries, the significant results in the pooled Caucasian sample imply an ethnic heterogeneity in -308G/A variation in the TNF-alpha gene in schizophrenia.