Overactivation of G-protein-mediated functions and altered G-protein regulation have been reported in bipolar disorder (BD) brain. Further, drugs effective in treating BD are reported to up-regulate expression of G-protein receptor kinase (GRK) 3 in rat frontal cortex. We therefore hypothesized that some G-protein subunits and GRK levels would be reduced in the brain of BD patients. We determined protein and mRNA levels of G-protein beta and gamma subunits, GRK2, and GRK3 in post-mortem frontal cortex from 10 BD patients and 10 age-matched controls by using immunoblots and real-time RT-PCR. There were statistically significant decreases in protein and mRNA levels of G-protein subunits beta and gamma and of GRK3 in BD brain but not a significant difference in the GRK2 level. Decreased expression of G-protein subunits and of GRK3 may alter neurotransmission, leading to disturbed cognition and behaviour in BD.