Haberberger, Rainer, Michael Schemann, Holger Sann, and Wolfgang Kummer. Innervation pattern of guinea pig pulmonary vasculature depends on vascular diameter. J. Appl. Physiol. 82(2): 426-434, 1997.The pulmonary vasculature is supplied by various neurochemically distinct types of nerve fibers, including sensory substance P-containing and autonomic noradrenergic, nitrergic, and cholinergic axons. Pharmacological experiments have suggested that various segments of the pulmonary vascular tree respond differently to the respective neuromediators. We, therefore, aimed to determine histochemically and immunohistochemically for each of these neurochemically distinct perivascular axons their quantitative distribution along the vascular tree from the extrapulmonary trunks to the smallest intraparenchymal ramifications in control guinea pigs (n = 5). Generally, arterial innervation was more developed than that of veins. Along the arterial tree, noradrenergic and substance P-containing axons were ubiquitous from the pulmonary trunk to smallest intraparenchymal vessels, whereas nitrergic axons were practically restricted to large (>700-µm) extrapulmonary arteries. Cholinergic axons were regularly present at arteries down to 100 µm in diameter and innervated two-thirds of small arteries (50-100 µm). The results demonstrate that the noradrenergic vasoconstrictor innervation extends throughout the pulmonary vascular system whereas the innervation pattern with various types of vasodilator fibers changes with vascular diameter, parallel to known pharmacological differences in cholinergic and nitrergic vasodilator effects.