A dysfunction in the intracellular signal transduction pathways may be implicated in the pathophysiology of bipolar disorder. In particular, the phosphatidylinositol (PI) signal transduction pathway may be a possible site of dysfunction. Platelets, peripheral cells, and post-mortem brain samples have been used as models in preliminary studies aimed at investigating this hypothesis. Emerging findings from clinical studies are consistent with a hyperfunction in the PI pathway in the manic state, which could be state-related. Findings of increased protein kinase C (PKC) activity in the manic state, and increased intracellular Ca2+ responsiveness in the manic and possibly depressed states, are also consistent with a hyperactive PI pathway in this disorder. Future research should attempt to replicate and extend these preliminary findings further.