1 Several thrombin cellular e ects are dependent upon stimulation of proteinase activated receptor-1 (PAR-1) localized over the cellular surface. Following activation by thrombin, a new Nterminus peptide is unmasked on PAR-1 receptor, which functions as a tethered ligand for the receptor itself. Synthetic peptides called thrombin receptor activating peptides (TRAPs), corresponding to the N-terminus residue unmasked, reproduce several thrombin cellular e ects, but are devoid of catalytic activity. We have evaluated the bronchial response to intravenous administration of human a-thrombin or a thrombin receptor activating peptide (TRAP-9) in anaesthetized, arti®cially ventilated guinea-pigs. 2 Intravenous injection of thrombin (100 u kg 71 ) caused bronchoconstriction that was recapitulated by injection of TRAP-9 (1 mg kg 71 ). Animal pretreatment with the thrombin inhibitor Hirulog TM (10 mg kg 71 i.v.) prevented thrombin-induced bronchoconstriction, but did not a ect bronchoconstriction induced by TRAP-9. Both agents did not induce bronchoconstriction when injected intravenously to rats. 3 The bronchoconstrictor e ect of thrombin and TRAP-9 was subjected to tolerance; however, in animals desensitized to thrombin e ect, TRAP-9 was still capable of inducing bronchoconstriction, but not vice versa. 4 Depleting animals of circulating platelets prevented bronchoconstriction induced by both thrombin and TRAP-9. 5 Bronchoconstriction was paralleled by a biphasic change in arterial blood pressure, characterized by a hypotensive phase followed by a hypertensive phase. Thrombin-induced hypotension was not subject to tolerance and was inhibited by Hirulog TM ; conversely, hypertension was subject to tolerance and was not inhibited by Hirulog TM . Hypotension and hypertension induced by TRAP-9 were neither subject to tolerance nor inhibited by Hirulog TM . 6 Our results indicate that thrombin causes bronchoconstriction in guinea-pigs through a mechanism that requires proteolytic activation of its receptor and the exposure of the tethered ligand peptide. Platelet activation might be triggered by the thrombin e ect.