In recent years changes in gene expression have been observed in postmortem brain tissue from individuals with schizophrenia using microarrays. In particular, significant changes have been reported in neuronal myelination, cellular signalling and presynaptic pathways. This study aimed to determine if similar changes in gene expression could be detected in peripheral blood lymphocytes from 14 individuals with schizophrenia and 14 non-psychiatric controls, matched for age and gender. cDNA microarrays consisting of 6,000 genes were used to identify genes with a fold change greater than 1.5 in peripheral blood lymphocytes. The level of expression for 123 genes was significantly altered in schizophrenia for more than half of the matched pairs, 5 of which were confirmed using Real-time PCR. Confirmed changes were found in genes associated with myelination, metabolism, neurotransmitter receptor regulation and damage recognition in the CNS. Some of these results are consistent with previous reports from post-mortem brain tissue studies suggesting these pathways may be involved in the pathogenesis of schizophrenia. Further studies of these genes are required in individuals with schizophrenia, including investigation of the effects of anti-psychotic drugs. In conclusion, this study shows peripheral blood lymphocytes can be used to indicate gene expression changes in schizophrenia that may be useful in the development of a biological basis for diagnosing this disorder.