In contrast to the majority of sympathetic neurons which are noradrenergic, the sympathetic neurons which innervate sweat glands are cholinergic. Previous studies have demonstrated that during development the sweat gland innervation initially contains catecholamines which are lost as cholinergic function appears. The neurotransmitter phenotype of sweat gland neurons further differs from the majority in that they contain vasoactive intestinal peptide (VIP) rather than neuropeptide Y (NPY). In the experiments described here, we addressed the question of whether sympathetic targets influence the neurotransmitter-related properties of the neurons which innervate them; in particular, do sweat glands play a role in reducing the expression of noradrenergic properties and inducing the expression of cholinergic properties and VIP in sympathetic neurons? This was accomplished by cotransplanting to the anterior chamber of the eye of host rats the superior cervical ganglia (SCG) which contains neurons that normally innervate targets other than the sweat glands and differentiate noradrenergically and footpad tissue from neonatal rats. Sweat glands developed in the transplanted footpad tissue and became innervated by the cotransplanted SCG neurons. The transplanted neurons and sweat gland innervation initially exhibited catecholamine histofluorescence which declined with further development in the anterior chamber. After 4 weeks, choline acetyltransferase (ChAT) and VIP immunoreactivities were evident. These observations suggest that as in the neurons which innervate the glands in situ, noradrenergic properties were suppressed and cholinergic function was induced in the neurons which innervated the glands in oculo. To distinguish a specific influence of the sweat glands on transmitter choice, SCG were also cotransplanted with the pineal gland, a normal target of the ganglion. Neurons cotransplanted with the pineal gland continued to exhibit catecholamine histofluorescence and contained NPY immunoreactivity. At least some neurons in SCG/pineal cotransplants, however, developed ChAT immunoreactivity. The target-appropriate expression of catecholamines and peptides in these experiments is consistent with the hypothesis that some transmitter properties are influenced by target tissues. The indiscriminant expression of ChAT, however, suggests that at least in oculo, additional factors can influence transmitter choice.