Histamine receptors on guinea-pig ileum submucosal arterioles (outside diameter 40–80 μm) were studied in vitro using a computer-assisted videomicroscopy system (Diamtrak ®). Histamine receptor agonists investigated in this study were histamine, the H 1 receptor-selective compound, 2-[2-(3-fluorophenyl)-4-imidazolyl]ethanamine (VZ 20), the H 2 receptor-selective compounds, dimaprit, impromidine, (±)-N 1 [3-(4-fluorophenyl)-3-(pyridin-2-yl)propyl]-N 2-[3-(1H-imidazol-4-yl)Dpropyllguanidine (arpromidine) and (±)-N 1-[3-(3,4-difluorophenyl)-3-(pyridin2-yl)propyl]-N 2-[3-(1H-imidazol-4-yl)propyl]guanidine (BU-E-75), as well as the H 3 receptor-selective drug, (R)-α-methylhistamine ((R)-α-MeHA). Applied to vessels at resting tone, the agonists (1 nM-300 μM) did not change arteriolar diameter. Vessels prcconstrictcd by 10 μM noradrenaline showed similar concentration-dependent vasodilations with histamine and VZ 20 (pD 2 = 5.38 and 5.36, respectively). This histamine-induced vasodilation was not affected by tetrodotoxin (0.5 μM) or indomethacin (1 μM). but was completely abolished in the presence of 1μM of the H 1 receptor antagonist, mepyramine. Calculation of the antagonist affinity of mepyramine for the histamine receptors in submucosal arterioles yielded a pA 2 of 9.46. In contrast to histamine and VZ 20, the H 2 receptor agonist, dimaprit, and the H 3 receptor agonist, (R)-α-MeHA, were ineffective at preconstrictcd arterioles. The guanidine-type H 2 receptor agonists, impromidine, arpromidine and BU-E-75, produced vasodilation at noradrenaline-preconstricted arterioles (−log (EC 50 = 4.47, 5.30 and 5.39, respectively) but, in contrast to histamine, were ineffective at arterioles preconstricted by U-46619 (300 nM). The −log EC 50 were significantly correlated to antagonist affinities (pA 2 values) of the compounds determined at α 1-adrenoceptors in rat vas deferens and using urapidil as reference α 1-receptor antagonist (impromidine = 4.73, arpromidine = 5.66 and BU-E-75 = 6.15: urapidil pA 2 = 7.52 and −log EC 50) = 6.56 at guinea-pig ileum submucosal arterioles). Thus, vasodilation due to the guanidine-typ H 2 receptor agonists in noradrenalinc-preconstricted arterioies was due to concomitant α 1-adrenoceptor antagonism of the compounds. The data suggest that submucosal arterioles in guinea-pig ileum possess only functional histamine H 1 receptois; activation of which dilates the blood vessels.