The effect of transferrin on phosphoinositide metabolism was investigated in smooth muscle cells isolated from the porcine basilar artery. Ferric iron-bound transferrin induced a rapid increase in the level of inositol phosphates, the metabolic products of phosphoinositides through the phospholipase C pathway. Neither transferrin free of ferric iron nor ferric iron alone caused the activation of phospholipase C. This study suggests that ferric iron-bound transferrin is capable of eliciting receptor-mediated signal transduction in porcine cerebral arterial smooth muscle cells, which could result in the contraction of smooth muscle cells. Transferrin may be involved with the cerebral arterial narrowing in pathological conditions such as subarachnoid hemorrhage.