We have used whole cell patch clamp recording and immunohistochemistry to investigate the expression of P2X2/3 receptors in rat superior cervical ganglion neurons during late embryonic and early post-natal development. Neurons from E18 and P1 animals responded to the nicotinic agonist dimethylphenylpiperazinium (DMPP), and the purinoceptor agonists ATP and α,β-meATP with sustained inward currents. Responsiveness to DMPP was maintained at P17, while that to ATP declined dramatically, and responses to α,β-meATP were rarely detected. Immunohistochemistry for the P2X3 subunit revealed widespread staining in superior cervical ganglia from P1 rats, but little immunoreactivity in ganglia from P17 animals. In neurons from P1 animals, the response to α,β-meATP exhibited pharmacological properties of the heteromeric P2X2/3 receptor. In conclusion, sympathetic neurons of the rat superior cervical ganglion are more responsive to ATP and α,β-meATP at birth and during the early post-natal period, due largely to the expression of the P2X3 subunit, but these responses are much reduced in mature rats. Developmental Dynamics 234:505–511, 2005. © 2005 Wiley-Liss, Inc.