We have recently described a unique cGMP-activated Ca² -activated chloride current (I_{Cl(cGMP, Ca)}) in smooth muscle cells (SMCs) (Matchkov et al. 2004) with properties distinct from the classical Ca² -activated chloride current (I_Cl(Ca)). In contrast to I_Cl(Ca), the new current is activated by cGMP via PKG. In the following table the properties of the classical I_Cl(Ca) and the novel I_{Cl(cGMP, Ca)} are compared. Interestingly, both currents were found to co-exist in smooth muscle cells, where they can be separated pharmacologically. We characterised the distribution of the I_{Cl(cGMP, Ca)} in vascular and non-vascular SMCs of different origin: aorta, pulmonary artery, tail artery, femoral artery, femoral vein, middle cerebral artery, renal artery, portal vein, superior mesenteric artery, mesenteric small artery and colon and compared distribution to that of classical I_Cl(Ca). The conventional patch-clamp technique was used. Rats were humanely killed, tissues were excised, and fresh SMCs were enzymatically isolated. We found that I_Cl(Ca) and I_Cl(cGMP,Ca) co-exist throughout the vascular tree, with the exception of the pulmonary circulation where only I_Cl(Ca) was found. I_{Cl(cGMP, Ca)} was dominant in cerebral artery and femoral vein, and was larger than I_Cl(Ca) in aorta, renal, femoral, mesenteric small and superior mesenteric arteries. I_Cl(Ca) was pronounced in portal vein and tail artery. I_{Cl(cGMP, Ca)} was also present in SMCs of colon (Matchkov et al. 2005). The present data point to the possibility that I_Cl(cGMP,Ca) may play a significant role in the regulation of vascular and potentially non-vascular smooth muscle. Selective inhibition of I_{Cl(cGMP, Ca)} inhibits vasomotion, demonstrating the essential role of this channel in synchronising cellular activity (Peng et al. 2001). This channel has all required properties to be a link between two major signalling pathways: calcium and NO/cGMP.