The present investigation was undertaken to examine whether there is an abnormality in the expression of α and βγ subunits of G proteins both at the transcriptional and translational level in postmortem brain of adult and teenage suicide subjects and whether these abnormalities are related to mental disorders or suicide per se. In addition, an attempt has been made to investigate whether these abnormalities are similar or dissimilar in teenage and adult suicide, because the etiology of teenage suicide may be different than that of adults. A significant decrease in both mRNA and protein levels of Gi2α and GOα and a significant increase in levels of Gsα-S were observed in prefrontal cortex of suicide subjects (n = 43) compared with non-psychiatric control subjects (n = 38). When subjects were grouped according to age, a significantly decreased expression of Gi2α and GOα and significantly increased expression of Gsα-S were observed in adult suicide subjects (age ≥ 20 yrs; n = 20) as compared with age-matched controls (n = 27). These changes were present in all adult suicide subjects regardless of psychiatric diagnosis. On the other hand, although there were no significant differences in any α or βγ subunits in teenage suicide subjects (age ≤ 19 yrs; n = 16) when compared with matched control subjects (n = 18); however, mRNA and protein levels of Gi2α and GOα were significantly decreased and of Gsα-S were significantly increased only in those teenage suicide subjects who had a history of mental illness (n = 11). Our results suggest that there are defects in the expression of selective G protein α subunits in prefrontal cortex of adult and teenage suicide subjects, which appear to be related to mental disorders. © 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.