Effects of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), chlorpromazine, prenylamine and N2-dansyl-L-arginine-4-tert-butylpiperidine amide on vascular smooth muscle contraction were compared by using helically cut strips of rabbit aorta. These compounds were apparently calmodulin antagonists in vitro. W-7 at a concentration of 1 .times. 10-4 M significantly antagonized the contractile responses of aortic strips to the same extent as seen with norepinephrine, serotonin, histamine, prostaglandin F2.alpha., angiotensin II and KCl. Addition of 1 .times. 10-4 M N-(6-aminohexyl)-1-naphthalenesulfonamide, an analog of W-7 which has no chloride molecule in the structure and possesses a lower affinity for calmodulin than W-7, did not antagonize aortic contractions. Chlorpromazine at a concentration of 1 .times. 10-6 M specifically antagonized the norepinephrine-, serotonin- and histamine-induced contractions, but did not antagonize the prostaglandin F2.ALPHA.-and angiotensin II-induced contractions. Inhibition by prenylamine of the contractile response of aortic strips to KCl was marked compared with the inhibition by this drug of the responses to other agonists. N2-dansyl-L-arginine-4-tert-butylpiperidine amide selectively antagonized the serotonin- and KCl-induced contractions at a concentration of 1 .times. 10-5 M. At this concentration responses to norepinephrine, histamine and prostaglandin F2.alpha. were not affected by the drug. Each calmodulin antagonist tested apparently had a different spectrum of action. Of these only W-7 has a specific interaction with calmodulin.