We investigated the expression of the N-methyl-D-aspartate (NMDA) receptor, an important glutamate receptor, in brains from a population of well characterized schizophrenic patients who prospectively consented to tissue donation. Levels of NR-1 mRNA in tissue homogenates of superior temporal cortex were reduced by 30% in cognitively impaired schizophrenic patients compared with controls (p < 0.04), while levels in patients without cognitive impairment showed no such reduction. The NR-1 mRNA deficit was significantly correlated with general cognitive function as rated with the Global Deterioration scale (p < 0.001), the Mini-Mental State examination (p < 0.01) and the premorbid IQ determined using the National Adult Reading Test (NART, p < 0.01). NR-1 mRNA concentration was not correlated with age, sex, pH or postmortem delay in the control and schizophrenia group when analysed separately or combined. There was, therefore, a significant correlation between NR-1 mRNA loss and cognitive deterioration in patients with schizophrenia.