Autonomic sympathetic postganglionic neurons normally express distinct combinations of neuropeptides which are often highly correlated with the projection of the neurons. When sympathetic postganglionic neurons are axotomized, they can express quite different neuropeptides, notably substance P, vasoactive intestinal peptide or galanin. In this study, we have examined rat sympathetic postganglionic neurons in the superior cervical ganglion that project to the skin, the vasculature of the skeletal muscle or to the submandibular salivary gland, and assessed whether the neuropeptides that they express after axotomy depend on which target tissue they previously innervated. In all three populations, around half of the postganglionic neurons expressed galanin after axotomy. In contrast, only skin-projecting neurons showed a significant increase in the number of neurons that expressed substance P (22%) and vasoactive intestinal peptide (17%) following axotomy. Within the skin-projecting neurons, as judged on the basis of cell body size, substance P and vasoactive intestinal peptide were expressed predominantly in pilomotor neurons, but only rarely were the two neuropeptides present in the same nerve cell body. In conclusion, we have demonstrated that three different neuropeptides, which can be induced by axotomy in postganglionic neurons, follow quite different patterns of expression when they are viewed in relation to the function of the postganglionic neurons in the superior cervical ganglion.