In the present study we evaluated the role of neurokinins in the modulation of inducible nitric oxide synthase (iNOS) inflammatory cell expression in guinea pigs with chronic allergic airway inflammation. In addition, we studied the acute effects of nitric oxide inhibition on this response. Animals were anesthetized and pretreated with capsaicin (50 mg.kg^-1 sc) or vehicle 10 days before receiving aerosolized ovalbumin or normal saline twice weekly for four weeks. Animals were then anesthetized, mechanically ventilated, given normal saline or N^G-nitro-L-arginine methyl ester (L-NAME 50 mg.kg^-1, ic) and challenged with ovalbumin. Pre-challenge exhaled NO increased in ovalbumin-exposed guinea pigs (p < 0.05 compared to controls) and capsaicin reduced this response (p < 0.001). When compared to animals inhaled with normal saline, ovalbumin-exposed animals presented increases in respiratory system resistance and elastance, and numbers of total mononuclear cells and eosinophils, including those expressing inducible NO synthase (iNOS) (p < 0.001). Capsaicin reduced all these responses (p < 0.05) except for iNOS expression in eosinophils. Treatment with LNAME increased post-antigen-challenge elastance and restored both resistance and elastance previously attenuated by capsaicin treatment. Isolated L-NAME administration also reduced total eosinophils and mononuclear cells, as well as those cells expressing iNOS (p < 0.05 compared to ovalbumin alone). Since L-NAME treatment restored lung mechanical alterations previously attenuated by capsaicin, NO and neurokinins may interact in controlling airway tone. In this experimental model, NO and neurokinins modulate eosinophil and lymphocyte infiltration in the airways.