An important hypothesis of vascular specificity is that a vessel's phenotype is determined by the target tissue being vascularized rather than by the source of the vessel. We have found-an exception to this hypothesis. When autografts of skeletal muscle are placed in the choroid plexus of the IV ventricle, some of the vessels that grow into the target muscle graft are not of the muscle type but, rather, of the source: the fenestrated vessels of the choroid plexus. This exception is most apparent and frequent, for unknown reasons, in those rats from which both superior cervical ganglia had been removed in order to ascertain the source of the grafts' innervation. In 4 of 5 ganglionectomized rats, some of the vessels that grew among muscle fibers of the graft, were not of the muscle type but rather fenestrated, like those of the choroid plexus. The source, not the milieu of the target muscle tissue, had determined the structural phenotype of the muscle. In order to see whether the mature graft tissue had lost its ability to induce vessel changes, 18-day-old fetal muscle is being grafted. It is likely that the hypothesis is valid when both the target and source tissues are fetal.