The effect of estrogen and progesterone on the reactivity of isolated rabbit saphenous veins to adrenergic stimulation by norepinephrine, methoxamine, phenylephrine, and electrical stimulation and the effect of progesterone on the reactivity to barium ions were studied. 8 days after ovariectomy, a saphenous vein was removed and studied in vitro. After 1 and 4 days of hormone therapy, the contralateral vein was removed and its reactivity was compared with that of the first vein and with that of veins from untreated, sham-operated control animals. The reactivity to adrenergic and nonadrenergic stimulation was increased after 4 days of treatment with progesterone (5 mg/day); treatment for 4 days with estrogen (100 µg/day) increased the reactivity to norepinephrine, electrical stimulation, methoxamine, and phenylephrine. The results with progesterone suggest that the increased adrenergic responsiveness is not related to a mechanism controlling adrenergic transmission in veins.