In the lymphatic vessels of man and most animals the nerve fibers are confined to the adventitia. However, immunohistochemical studies suggest that acetylcholinesterase-positive and monoamine-containing fibers reach as far as the endothelium in bovines. The aim of this study was to verify the presence of subendothelial nerve fibers by transmission electron microscopy (TEM) in bovine mesenteric lymphatics and to determine whether typical sensory neurotransmitters such as Substance P (SP) and calcitonin gene related peptide (CGRP) could be detected in these fibers. TEM revealed numerous unmyelinated nerve fibers in the subendothelial connective environment in close association with endothelial cells. Their axons were devoid of Schwann cell sheath on the endothelial side and contained small clear vesicles and large nerve fibers were demonstrated to be SP and CGRP-immunoreactive with mouse monoclonal antibodies against SP and rabbit polyclonal antibodies against CGRP. It is hypothesized that these fibers act as mechanoceptors capable of detecting intraluminal pressure and vessel wall tension variations and of locally releasing SP and CGRP. Since SP, potentiated by CGRP, is known to be a vasoconstrictor in lymphatics, we propose that the contraction of bovine mesenteric lymphatics may also be neurogenic.