Schizophrenia is a devastating psychiatric disease that affects up to 1% of the population worldwide. Recent studies suggested that schizophrenia might result from the hypofunction of glutamatergic neurotransmission. Systematic positional, expression and functional studies have implicated the regulator of G-protein signaling 4 (RGS4) and proline dehydrogenase (PRODH) genes as promising and novel candidates for explaining schizophrenia. However, the findings of association studies tend to vary depending on the different populations on which they have been conducted. To reconcile this conflict of evidence, we combined all available population-based and family-based studies up to July 2005 involving eight polymorphisms. However, this meta-analysis did not find statistically significant evidence for association between the two glutamate-related genes and schizophrenia on the basis of either allelic or genotypic analysis. This may be the first systematic meta-analysis study based on RGS4 and PRODH.