It is well established that Ca²⁺-permeable non-selective cation channels have an important role in smooth muscle function. For example, many studies in diverse smooth muscle preparations have shown that agonist-induced excitatory responses involve non-selective cation channels which may also contribute to the resting membrane conductance. The purpose of this presentation is to describe the transduction pathways regulating these ion channels in freshly dispersed vascular smooth muscle cells. It will be shown that the non-selective cation current evoked by noradrenaline in rabbit portal vein involves G-protein stimulation of phospholipase C (PLC) and both diacylglycerol (DAG) and inositol 1,4,5-trisphosphate are required for optimal activation of the channel (a member of the tranisent receptor potential family, TRPC6). In rabbit ear artery cells there is a constitutively active non-selective cation channel which contributes to the resting membrane conductance but is also enhanced by noradrenaline. Like the portal vein DAG is implicated in channel activation by a protein kinase C (PKC)-independent mechanism. However, a striking difference between the two preparations is that PLC is involved in the inhibitory regulation of this channel and that phospholipase D activity produces DAG via phosphatidic acid to produce channel opening. It is evident that this class of non-selective cation channel is linked to diverse transduction pathways.