Ascorbate (Asc) has previously been shown to enhance both alpha-1 and beta-2 adrenergic activity. This activity is mediated by ascorbate binding to the extracellular domain of the adrenergic receptor (AR), which also decreases the oxidation rate of ascorbate. H1 histamine receptors (HR) have extracellular agonist/ascorbate binding sites with strong similarities to alpha-1 and beta-2 AR. Physiological concentrations of ascorbate (50 µM) significantly enhanced histamine contractions of rabbit aorta on the lower half of the histamine dose-response curve, increasing contractions of 0.1, 0.2 and 0.3 µM histamine by 2-3 fold. Increases in ascorbate concentration significantly enhanced 0.2 µM histamine (5-500 µM Asc) and 0.3 µM histamine (15-500 µM Asc) in a dose-dependent manner. Histamine does not measurably oxidize over 20 hours in oxygenated physiological salt solution at 37C. Thus, the ascorbate enhancement is independent of ascorbate’s anti-oxidant effects. Ascorbate in solution oxidizes rapidly. Transfected histamine receptor membrane suspension (HRM) with protein concentration at > 3.1 µg/ml (56 nM maximum HR) decreases the oxidation rate of 392 µM ascorbate, and virtually no ascorbate oxidation occurs at > 0.0004 mole HR/mole ascorbate. HRM had an initial ascorbate oxidation inhibition rate of 0.094 min^-1/µg protein/ml, compared with rates for transfected Angiotensin II membrane 0.055, untransfected membrane 0.052, Creatine Kinase 0.0082, Keyhole Limpet Hemocyanin 0.00092 min^-1/µg protein/ml, and osmotically lysed aortic rings 0.00057 min^-1/µg wet weight/ml. Ascorbate enhancement of seven-transmembrane spanning membrane receptor occurs in both adrenergic and histaminergic receptors. These receptors may play a significant role in maintaining extracellular ascorbate in a reduced state.