Dopamine and cyclic adenosine 3':5'-monophosphate (AMP)-regulated phosphoprotein, relative molecular mass 32,000 (DARPP-32), plays an important role in modulating the functions of various neurotransmitter systems. To explore the alterations in DARPP-32 in subjects with schizophrenia and bipolar disorder, we employed immunohistochemical and Western blotting techniques and examined the distribution and expression of DARPP-32 in the postmortem dorsolateral prefrontal cortex (DLPFC) from 12 subjects with schizophrenia, 10 subjects with bipolar disorder, and 11 control subjects. Immunohistochemical study demonstrated that DARPP-32 immunolabeling in the neuronal soma from subjects with schizophrenia and bipolar disorder was lower than in that from the controls. The results of the immunoblot analysis were consistent with those of the immunohistochemistry, and the amount of DARPP-32 in subjects with schizophrenia and bipolar disorder was found to be lower than that in the control subjects. The present study suggests that DARPP-32 decreases in the DLPFC of patients with schizophrenia and bipolar disorder, and further suggests that this decrease is associated with dysfunction of dopaminoceptive neurons in the DLPFC of patients affected by these two mental disorders.