1Pressor responses to arginine vasopressin (AVP) were determined in the rat isolated superior mesenteric arterial bed perfused with Krebs-Henseleit solution and compared with those to noradrenaline. 2 In control preparations the maximum pressor response to the peptide was 34 + 3 mmHg and the ED50 was 21 + 4 mu (n = 11). The maximal pressor response to noradrenaline (30 pg) was 100 + 6 mmHg (n = 8). After removal of the functional endothelium with the detergent CHAPS, the maximum pressor response to AVP increased to 64 + 4 mmHg and the ED50 decreased to 7.7 + 2.0 mu (n = 11) but the response to 10Oug noradrenaline was unaffected. 3 Nordihydroguaiaretic acid (2.5pM) significantly increased the maximum pressor response to AVP from 41 + 2 mmHg to 86 + 8 mmHg (n = 9); the ED50 was unchanged. Methylene blue (50 pM) also increased the maximum response from 41 + 3 mmHg to 87 + 13 mmHg (n = 8) without affecting the ED50. Neither treatment significantly affected the response to lOpg noradrenaline.4 Neither indomethacin (1OpM) nor BW755C (1OpM) had significant effects upon either the maximal response or ED50 for AVP nor did they affect the response to lOpg noradrenaline. 5 In 6 preparations SKF-525A significantly increased both the ED50, from 9.8 + 2.1 to 22 + 2 mu, and the maximum response, from 36 + 2 to 70 + 3 mmHg. 6 It is concluded that the pressor response to AVP in this vascular bed is modulated, in the presence of functional endothelium, by the simultaneous release of endothelium-derived relaxing factor.