The involvement of tachykinin NK1 receptors in the plasma protein extravasation (measured by the Evans blue leakage technique) produced by intravenous administration of capsaicin was investigated in the urinary bladder and trachea of anesthetized rats. Capsaicin-induced plasma extravasation was markedly inhibited by (+/-)-CP-96,345, a novel and potent non-peptide antagonist of tachykinin NK1 receptors. The same dose of (+/-)-CP-96,345 markedly inhibited the plasma protein extravasation induced by the selective NK1 receptor agonist, [Sar9]substance P sulfone, but had no effect on the response to histamine.