Catechol‐o‐methyltransferase (COMT) and proline dehydrogenase (PRODH) may both be susceptibility genes for schizophrenia. As part of the evaluation of their roles in psychosis, we used reverse transcription–polymerase chain reaction to measure COMT and PRODH mRNAs in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, major depression, and normal controls (n = 15 subjects in each group). We also genotyped two common COMT polymorphisms (–287A/G and 158Val/Met) which might affect its expression. Neither COMT nor PRODH mRNA abundance differed between diagnostic groups, nor when controls were compared with all psychotic patients. COMT mRNA levels were unrelated to COMT genotypes. We conclude that any involvement of COMT and PRODH genes in schizophrenia is not accompanied by significant alterations in their overall mRNA expression, at least in dorsolateral prefrontal cortex. As COMT and PRODH are both located on chromosome 22q11, the results also argue against the hypothesis that schizophrenia is associated with a decrease in expression of all 22q11 genes, as had been suggested by the high prevalence of psychosis in people with hemizygous 22q11 deletions. Synapse 51:112–118, 2004. © 2003 Wiley‐Liss, Inc.