The ultrastructural localization of substance P (SP) immunoreactivity, especially the morphology, number and distribution of positive large granular vesicles (LGV) in SP axon terminals of the trigeminal subnucleus caudalis of the rat were studied by electron microscopic immunocytochemistry. This study revealed that SP immunoreactivity was mostly located in axon terminals and unmyelinated fibers. SP axon terminals contained both clear round vesicles and LGV. SP immunoreactivity was found in LGV, and on the surface of clear round vesicles and outer membrane of mitochondria. Positive LGV were spherical or oval in shape (60～120nm in diameter). The number of LGv was mostly 2～3 in a SP axon terminal. LGV often apposed to the axolemma or scattered in the centre of terminal. LGV were far from the presynaptic sites of the SP terminals which formed synapses. The number of LGV closed to the terminal membrane was significantly (P

Previous studies have demonstrated that exocytotic release from large dense cored vesicle(LDV)at structurally non-specialized areas within axon terminal of the medullary dorsal horn and it has been speculated that non-synaptic exocytosis from LDV may be a probable mechanism for neuropeptide release. This study provides the evidence that SP containing LDV can release their contents by exocytosis at non-synaptic sites of axon terminal within superficial dorsal horn of medulla oblongata in the rat with ultrastructural immunohistochemistry staining by an unilateral deafferentation. The results of this study confirmed previous hypothesis that SP and perhaps other peptides containing LDV release their contents by exocytosis at non-specialized sites and the significance of such release is discussed.