The psychotomimetic properties of NMDA glutamate receptor antagonists suggest there may be disease related changes of this receptor in schizophrenia. Using in situ hybridisation histochemistry (ISHH), we measured mRNA for the obligatory NMDAR1 subunit of the NMDA glutamate receptor in post-mortem samples of hippocampus from schizophrenics, depressives, bipolar patients and normal controls. A significant main effect of diagnosis was observed in the dentate gyrus (ANOVA, p= 0.004) and a trend in the CA3 region (ANOVA, p= 0.06), with all psychiatric groups having reduced NMDAR1 mRNA levels compared to normal controls. In contrast to the affectively ill groups, the reductions in schizophrenics were more pronounced in the left side compared to the right. Expression of poly A mRNA also showed left-sided losses in the dentate gyrus in schizophrenia but reductions in NMDAR1 remained significant when expressed as a ratio of poly A. The findings confirm a recent report of reduced hippocampal NMDAR1 mRNA in schizophrenia. However, our new evidence suggests that this is a feature of both affective and schizophrenic disorders and that schizophrenia is distinguished from the others by left-sided reductions in hippocampal NMDAR1 gene expression.