Endogenously produced nitric oxide is a recognized regulator of physiological lung events, such as a neurotransmitter and a pro-inflammatory mediator. We tested the differences between chronic and acute nitric oxide inhibition by N-nitro-L-arginine methyl ester (L-NAME) treatment in lung mechanics, inflammation and airway remodeling in an experimental asthma model in guinea pigs. Both acute and chronic L-NAME treatment reduced exhaled nitric oxide in sensitized animals (p <0.001). Chronic L-NAME treatment increased baseline and maximal responses after antigen challenge of respiratory system resistance and reduced peribronchial edema and mononuclear cells airway infiltration (p <0.05). Acute administration of L-NAME increased maximal values of respiratory system elastance and reduced mononuclear cells and eosinophils in airway wall (p <0.05). Chronic ovalbumin exposure resulted in airway wall thickening, due to an increase in collagen content (p <0.005). Chronic nitric oxide inhibition increased collagen deposition in airway wall in sensitized animals (p <0.05). These data support the hypothesis that in this model, nitric oxide acts as a bronchodilator, mainly in proximal airways. Furthermore, chronic nitric oxide inhibition was effective in reducing edema and mononuclear cells in airway wall. However, airway eosinophilic inflammation was unaltered by chronic L-NAME treatment. In addition, nitric oxide inhibition up-regulates collagen deposition in airway walls.