The purpose of this study was to determine whether tannic acid elicits neurogenic plasma exudation from the oral mucosa in vivo and, if so, whether this response is transduced in part by the L-arginine-nitric oxide (NO) biosynthetic pathway. Using intravital microscopy, we found that suffusion of tannic acid elicits significant concentration-dependent leaky site formation and increase in clearance of fluorescein isothiocyanate-dextran (molecular mass 70 kDa) from the in situ hamster cheek pouch (P < 0.05). These effects are significantly attenuated by two selective, but structurally distinct, nonpeptide neurokinin-1 (NK₁) receptor antagonists, CP-96,345 and RP-67580, but not by CP-96,344, the 2R,3R enantiomer of CP-96,345. N^G-nitrol-arginine methyl ester (L-NAME), an NO synthase inhibitor, but not D-NAME, significantly attenuates tannic acid-induced responses. L-Arginine, but not D-arginine, reverses the attenuating effects of L-NAME. We conclude that tannic acid elicits L-arginine-NO biosynthetic pathway-dependent neurogenic plasma exudation from the in situ hamster cheek pouch.