Schwann cells, from a variety of sources, are known to possess P2Y purinergic metabotropic receptors. However, it is not known if Schwann cells associated with autonomic nerve terminals possess such receptors and if so whether these receptors are activated by the endogenous release of ATP from the nerve terminals. We show that such Schwann cells in the vas deferens give evoked calcium transients on nerve stimulation. These transients are mediated, at least in part, by the endogenous release of ATP, which acts on Schwann cell P2Y receptors to release calcium from within the cells. This work suggests the possibility that Schwann cells are active participants in the process of junctional transmission in the autonomic nervous system.