To determine whether sympathetic axons require the presence of a peripheral target to grow to the correct destination, we examined the developing footpad innervation in tabby mutant mice which lack sweat glands. Despite the absence of sweat glands, noradrenergic sympathetic axons are transiently present in the presumptive target area and avoid the more distal epidermal/dermal domain occupied by sensory axons. Since sympathetic axon pathfinding was not dependent upon the target tissue, we compared the subsequent development of sweat gland axons in tabby footpads with that in control footpads. In wild-type mice, the gland-associated axonal plexus expands considerably as the secretory tubule enlarges and coils. This expansion, however, does not occur in tabby mice. The sweat gland innervation of wild-type mice loses catecholamines and acquires AChE activity and vasoactive intestinal peptide immunoreactivity. In tabby mutant mice, catecholaminergic fibers remain in the glandless footpads for 2 weeks and fail to acquire AChE or vasoactive intestinal peptide. In contrast to the altered development of gland innervation in tabby, the development of the innervation of footpad blood vessels was unaffected. Our observations indicate that the target is not required to direct sympathetic axons to the presumptive gland region of the footpad. In the absence of the target tissue, however, gland-targeted sympathetic axons retain an immature morphology and transmitter phenotype and then disappear.