OBJECTIVE: Previous investigations have suggested the involvement of signal-transducing guanine-nucleotide-binding proteins (G proteins) both in the mechanism of action of lithium and in the pathophysiology of bipolar affective disorder. To determine whether such G protein abnormalities are a trait phenomenon, the authors investigated the levels of G protein alpha subunits in platelets and lymphocytes of euthymic patients with bipolar affective disorder. METHOD: Selective antibodies were used to quantitate levels of G protein alpha subunits regulating adenylylcyclase activity (Gs alpha-both 45- and 52-kDa forms- and Gil-2 alpha) and those regulating phosphoinositide turnover (Gq/11 alpha) in both platelets and lymphocytes of 44 euthymic patients with bipolar affective disorder and 27 matched comparison subjects. RESULTS: Levels of both Gs alpha 45 and Gs alpha 52 were higher in the platelets of the euthymic bipolar patients (both bipolar I and bipolar II) than in those of the comparison subjects. CONCLUSIONS: These findings are consistent with previous reports of high Gs alpha levels in bipolar affective disorder and, furthermore, suggest that such levels may be a trait abnormality for this condition.