Phenylpropanolamine (PPA) is a sympathomimetic drug that exerts its effect mainly through the alphaadrenergic receptor. A pharmacoepidemiological study reported by the hemorrhagic stroke project in the year 2000 suggested an association between high dose PPA and hemorrhagic stroke. However, the hemodynamic effect of PPA might be altered in the presence of chlorpheniramine (CPM) as used in over-the-counter cold remedy (PPA, 0.3 mg/kg plus CPM, 0.04 mg/kg). It was found that PPA (5-30 times that used in humans) dose-dependently increased in blood pressure in rats and this effect was antagonized by CPM in male rats and non-proestrous female rats but not in proestrous female rats. The hypertensive effect of PPA could not be antagonized by loratadine, a highly specific H1 blocker.