In searching for genes dysregulated in schizophrenia, we measured the expression of the two splice variants of calcium/calmodulin-dependent protein kinase II (CaMKIIα and CaMKIIβ) in postmortem frontal cerebral cortex tissues from patients who had died with schizophrenia, bipolar disorder, or severe depression. The mRNA levels of expression of these two splice variants were measured by real–time Quantitative PCR, using an Mx4000 instrument. The values for the expression of CaMKIIα and CaMKIIβ were normalized by the expression of β-glucuronidase in the tissues. The expression of CaMKIIα was significantly elevated in the depression tissues by 29%. The expression of CaMKIIβ was significantly elevated in the schizophrenia tissues by 27%, and in the depression tissues by 36%. Because CaMKIIβ influences the expression of many neuroreceptors and influences neural outgrowth and pruning, its altered expression in the cerebral cortex in schizophrenia or depression may contribute to these diseases. Synapse 59:61–68, 2006. © 2005 Wiley-Liss, Inc.