Quantitative and functional measurements of G proteins were undertaken in mononuclear leukocytes of bipolar disordered patients comparing bipolar depressed with manic patients groups in order to verify whether any alterations observed in G protein functional or immunoreactive measures in bipolar mood disorder are state- or trait-dependent characteristics. Compared with the control group of 30 subjects, isoproterenol- and carbamylcholine-enhanced Gpp(NH)p binding capacities were highly significantly increased in the group of 20 manic patients, while highly significantly reduced in the group of 11 bipolar depressed patients. While manic patients showed highly significant elevations in mononuclear leukocytes levels of G alpha s and G alpha i, evaluated through immunoblot analysis using specific polyclonal antibodies against the subunit proteins, mononuclear leukocytes of bipolar depressed patients show significant reductions in G alpha s and G alpha i immunoreactive levels. G beta subunit levels were found to be similar in all three groups. The changes in G protein measures observed in mononuclear leukocytes of mood disordered patients thus represent state characteristics of the disorder.