Within arterioles, endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) communicate via gap junctions at the myoendothelial junction (MEJ). This functional coordination is important for the control of blood flow, but little is known about how heterocellular communication is controlled. For instance, it is known that the transfer of the second messenger Ins(1,4,5)P3 from VSMCs modulates Ca2+ stores in ECs, whereas Ins(1,4,5)P3 that originates in ECs does not affect VSMC Ca2+ stores – but how is this directionality maintained? On page 3664, Brant Isakson addresses this question. Using an EC-VSMC co-culture system, the author shows that intercellular Ins(1,4,5)P3 signalling is not affected by modulating the connexin composition of gap junctions. Notably, however, the Ins(1,4,5)P3 receptor Ins(1,4,5)P3-R1 is selectively localised to the EC side of the MEJ, and knocking down the expression of the receptor abolishes the response to Ins(1,4,5)P3 in ECs. Moreover, VSMCs that are loaded with a phosphatase inhibitor respond to EC-generated Ins(1,4,5)P3. The author concludes that Ins(1,4,5)P3 transport at the MEJ is bidirectional but that, because of the position of the Ins(1,4,5)P3 receptor, only ECs mount a response before Ins(1,4,5)P3 is degraded. The MEJ might, therefore, act as a cellular signalling domain within the vasculature.