The purpose of this study was to determine whether an aqueous extract of grain sorghum dust (GDE) elicits neurogenic plasma exudation in the oral mucosa in vivo. Using intravital microscopy, we found that GDE elicited significant, concentration-dependent leaky site formation and an increase in clearance of fluorescein isothiocyanate-labeled dextran (FITC-dextran; mol mass 70 kDa) from the hamster cheek pouch (P < 0.05). The selective, nonpeptide neurokinin(1) (substance P) receptor antagonists, CP-96,345 and RP-67580, but not the 2R,3R enantiomer CP-96,344, significantly attenuated GDE-induced leaky site formation and increase in clearance of FITC-dextran (P < 0.05). Indomethacin had no significant effects on GDE-induced responses. CP-96,345 had no significant effects of adenosine-induced leaky site formation and increase in clearance of FITC-dextran from the cheek pouch. We conclude that GDE elicits neurogenic plasma exudation from the oral mucosa in vivo. We suggest that this process is one mechanism whereby grain sorghum dust elicits immediate oral mucosa inflammation in vivo.