A review of research on the relationship between the regulation of cellular sensitivity to drugs and transmitters and membrane potential is presented, with an emphasis on experiments with the rabbit saphenous artery. Chronic depression of the adrenergic innervation to the saphenous artery induces an adaptive and nonspecific increase in sensitivity which appears with a delay of 3 days. Coincident with the supersensitivity, the smooth muscle cells undergo a partial depolarization which brings the resting potential closer to the threshold potential for contraction. The evidence is that the depolarization is due to the loss of electrogenic Na+, K+ pumping and is the primary factor responsible for the supersensitivity.