We have employed anesthetized guinea pigs to examine effects of nonsteroidal antiasthma drugs on airway plasma exudation, which is a process of potential pathogenetic importance in asthma. This study focused on exudation of plasma into the airway luman (circumventing problems with a changing blood pool in tissue samples). Topical tracheal superfusions with a neurogenic agent (capsalcin), bradykinin, and histamine increased mucosal blood flow (Laser Doppler flowmetry) and produced significant exudation of macromolecular plasma tracers (fluorescein-labeled dextran 156000 D; 131I-albumin 70,000 D). Lidocaine 3 x 10(-5) M, applied topically, inhibited capsalcin- but not bradykinin-induced plasma exudation. Intravenously administered terbutaline, enprofylline, and theophylline and topical cromoglycate dose-dependently inhibited the inflammatory stimuli-induced mucosal exudation of plasma. Cromoglycate did not alter airway blood flow, and both terbutaline and enprofylline increased the blood flow. Hence, these three types of drugs did not inhibit exudation by stopping flow. Further, both neural and non-neural exudative responses were inhibited, suggesting that the drugs may have acted directly on the permeability-regulating microvascular endothelial cells. It is proposed that antiexudative actions may contribute to the antiasthma effects of beta 2-agonists, xanthines, and cromoglycates.