Schizophrenia (SZ) is a psychiatric disease with plausible neurodevelopmental etiology. Although genetic studies show significant association of immune molecules loci such as major histocompatibility complex (MHC) class I with SZ, it is not clear whether these immune molecules are involved in the pathology observed in SZ brains. MHC class I and the classical pathway components of complement system (C1q and C3) have been shown to regulate brain neuronal maturation and function. We have examined the expression of MHC class I and complement protein C3 in two frontal cortical regions of postmortem brains of SZ patients. Since cigarette smoking may modulate MHC class I protein expression and a higher rate of smoking is observed in SZ patients, we studied the expression of MHC class I and C3 in relation to the presence of smoking. We found that MHC class I protein expression is reduced in the dorsolateral prefrontal cortex (DLPFC) but not in the orbitofrontal cortex (OFC) of nonsmoker SZ patients. We did not observe SZ-associated changes in C3 mRNA expression. Our exploratory research suggests a potential involvement of MHC class I in SZ and implies that smoking might modulate its expression. © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society.