Potassium and hydrogen ion interactions have been reported in the pial vessels of the cerebral vasculature. Adenosine and hydrogen ion interactions were also found in the coronary circulation. We now report an interaction of perfusate pH and potassium in the coronary vasculature. Isolated, perfused guinea pig hearts were used to investigate the possible influence of perfusate pH on hyperkalemic vasodilation and on ouabain blockade of the coronary response to hyperkalemia. At perfusate pH 7.45, potassium infusion increased coronary diastolic flow 18%. At pH 7.21, the same concentration of potassium increased flow 35% above control. The coronary vascular response to potassium was modestly diminished at pH 7.65. The duration of the transient vasodilatory response to potassium at low pH was more than doubled relative to pH 7.45. The presence of ouabain in the perfusate significantly (p < 0.05) reduced the dilating action of potassium at pH 7.01 and 7.65. We conclude that the effect of hyperkalemia on coronary flow is pH sensitive but that ouabain blockade of the potassium response is not effected by changes in pH.