Nerve fibres immunoreactive for substance P (SP) and calcitonin gene-related peptide (CGRP) were located preferentially at the base of the junctional epithelium. Occasional fibres were observed in close proximity to the subepithelial, small blood vessels. The vascular connective tissue papillae projecting into the epithelium were more densely surrounded by SP- and CGRP-immunoreactive fibres in the interdental col than in other regions of the gingiva. In some cases, hyperplasia of the junctional epithelium was noted in the interdental col where the connective tissue papillae were invaded by widened vessels, indicating severe irritation. SP- and CGRP-immunoreactive fibres around these papillae showed increases in their immunoreactivity and thickness, with some fibres terminating as large expansions. Double immunohistochemical staining revealed the co-existence of SP and CGRP in all nerve fibres within and under the junctional epithelium. Capsaicin pretreatment eliminated most of the immunoreactivity for both peptides. Intravenous infusion of capsaicin or SP caused increased permeability in vessels underlying the junctional epithelium, as indicated by Monastral blue labelling. Labelled vessels were arranged not only in a network extending under the epithelium but also in loops protruding into the connective tissue papillae. These labelled vessels were most abundant in the interdental col, where vascular loops with more complex configurations exhibited strong staining in their walls. In the case of hyperplasia of the junctional epithelium in the interdental col, widened vessels showing extensive labelling in their walls were observed. In capsaicin-pretreated animals, capsaicin-induced extravasation was abolished, while the effect of SP was still observed. These findings provide evidence that capsaicin-sensitive sensory nerves supplying the junctional epithelium are involved in neurogenic plasma extravasation in the rat gingiva. The enhancement of neurogenic plasma extravasation in the col may be vascular response associated with a higher susceptibility of this region to gingival inflammation.