Evidence was obtained for a previously unidentified form of sensitization in vascular smooth muscle related to calcium utilization. The quaternary ammonium compound tetraethylammonium potentiated the amplitude of contractions elicited by a variety of agonists in rabbit aortic strips. The potentiating effect was not reduced in strips from rabbits pretreated with reserpine to deplete endogenous catecholamine. An analysis of the mechanism of enhancement indicated that tetraethylammonium increased the utilization of extracellular and/or loosely bound calcium for contraction. It was found that potentiation was much reduced and usually blocked in a low-calcium solution. In addition, SKF-525A, a substance that inhibits selectively the influx of extracellular calcium to the contractile elements, generally abolished enhancement. Effects on calcium utilization should be considered as a possible mechanism in other currently undefined potentiations.