Glycogen synthase kinase (GSK)-3beta is a conserved serine/threonine protein kinase highly abundant in brain tissue. A dominant mechanism by which cells react to stress involves GSK-3beta. We studied the effect of stress on GSK-3beta levels ex vivo. We have previously found reduced GSK-3beta protein levels and GSK-3 activity in postmortem prefrontal cortex of schizophrenic patients. Since schizophrenic patients experience stress more severely than healthy people, we questioned whether their GSK-3beta reduction is stress-related using a rat model. Rats were exposed to acute, subchronic, or chronic stress using brief cold restraint. No effect was found on frontal cortex GSK-3beta protein levels. These results suggest that reduction in GSK-3beta levels in schizophrenic patients is not affected by cold restraint stress and supports the possibility that the changes observed in postmortem brains may be related to the disease.