We have been examining how sympathetic neurons chose the neurotransmitters that they will use and how target tissues acquire the appropriate complement of receptors and effector proteins. Descriptive studies from our laboratory have delineated a developmental change in neurotransmitter phenotype from noradrenergic to cholinergic in the sympathetic innervation of sweat glands in rodent footpads. Transplantation and culture experiments provide evidence that interactions with the traget tissue induce this change. As part of our continuing analysis of synapse formation in the sweat gland system, we have examined albino mice which lack tyrosine hydroxylase and catecholamines and determined that the early catecholaminergic innervation plays a critical role in triggering the onset of secretory responsiveness in developing glands. We have identified a second target of cholinergic sympathetic neurons, the periosteum. Analysis of the transmitter properties of the developing periosteal innervation coupled with transplantation studies provide evidence that these sympathetic neurons, like those that innervate sweat glands, undergo a target- directed transmitter switch. Innervation of the vasculature in limb skeletal muscle has been proposed as a third target of cholinergic sympathetic neurons. We find, however, that there are no cholinergic phenotypic markers expressed by the innervation of the muscle vasculature. We have also examined the trophic factor responsiveness of developing sympathetic neurons in vivo. We find that approximately half of postmitotic sympathetic neurons require NT-3 in addition to NGF. To determine the function of the low affinity neurotrophin receptor in sympathetic neuron development, we examined mice which lack this receptor. Our data suggest that the principal role of the receptor is to sharpen the specificity of trkA for NGF. - synapse formation, autonomic nervous system, neurotransmitter plasticity, neurotrophins, transmitter receptors neuropoietic cytokines