Bipolar disorder is associated with increased levels and function of the G-protein, Gs alpha which may be normalized by treatment with mood stabilizing medications (i.e. lithium salts and the anticonvulsants, valproic acid and carbamazepine). In C6 glioma cells, endogenous ADP ribosylation was markedly increased by lithium chloride (+83%, P < 0.005), decreased by valproic acid (-48%, P = 0.07) whereas carbamazepine had no effect. Since ADP ribosylation of Gs alpha has been shown to increase turnover of this protein these results suggest a possible mechanism of action for lithium chloride. These results also suggest that lithium salts and the anticonvulsant mood stabilizers may have distinct mechanisms of action.