The musculotropic action of dicyclomine hydrochloride in bladder muscle has been attributed to its local anesthetic activity. In this study rabbit detrusor strips were depleted of calcium by incubation in Ca2+-free solution containing ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA). Contractions elicited by replacement of Ca2+ during depolarization with 80 mM K+ were only slightly affected by atropine or scopolamine but were antagonized in a noncompetitive manner by dicyclomine and rociverine (pD2' = 4.89 and 4.61, respectively). These contractions were also blocked with greater potency by nifedipine (pD2' = 8.50) and with lesser potency by lidocaine (pD2' = 2.52). Procaine was ineffective up to 1 mM. Comparison of the antagonism produced by dicyclomine and rociverine with that produced by nifedipine or lidocaine did not help to define the mechanism of the musculotropic drugs. However, as rociverine is not a local anesthetic and procaine was not effective, it appears that the "local anesthetic" property is not sufficient to explain the action of these musculotropic drugs.