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The effects of the H3 agonist (R) alpha-methyl histamine ( (R) alpha-MeHA) on the isolated guinea pig aorta were investigated. At all the concentrations of (R) alpha-MeHA used, a relaxation of the aorta, which had been preconstricted with KC1 (50mM), was produced. This response was abolished by the H3 antagonist mixture of cimetidine (100 microM) and impromidine (10 microM). In contrast the same concentrations of histamine produced vasoconstriction which could be abolished by the H1 antagonist pyrilamine (3 microM). The results show that (R) alpha-MeHA produces a vasodilation response which is most probably mediated by H3 receptors and provides further evidence of a functional role for H3 receptors in the control of the cardiovascular system.