VIP (6-28) (HUMAN, BOVINE, PORCINE, RAT) is an effective VIP antagonist in the superior cervical ganglion (SCG) , and results obtained using this analog indicate that endogenous VIP can participate in a positive feedback loop in injured sympathetic neurons in which it enhances its own expression. VIP(6-28), when added to short-term cultures of adult SCG at a concentration of 10, 30, or 100 μM, reduces the increase in cAMP levels produced by stimulation with 10 μM VIP by 52, 64, or 81%, respectively. At any of these concentrations tested, VIP(6-28) by itself does not alter cAMP levels. In contrast to its ability to reduce the VIP-stimulated elevation in cAMP levels by 64%, the addition of 30 μM VIP(6-28) to culture medium does not significantly alter cAMP levels measured after stimulation of adult ganglia with either isoproterenol or forskolin (10 μM each). Similar results on the ability of VIP(6-28) to block VIP -stimulated increases in cAMP levels are obtained in neuron-enriched and in non-neuronal cell-en riched dissociated cultures.