The maximum contractures evoked by 100 microM ACh of mouse soleus muscles denervated for 3-7 days are completely inhibited by a 10 min exposure to 100 microM chlorpromazine (CP). Recovery on washout of CP takes more than 1 hr to complete. ACh evoked contractures are also inhibited by diltiazem (D); washout of D is immediately followed by recovery. Electrically evoked twitches and K evoked contractures are largely unaffected by CP, caffeine evoked contractures are decreased but not abolished. Fast mouse and (non-denervated) frog tonic muscles behave similarly. Depolarization by ACh and ACh-evoked whole cell currents show enhanced desensitization at low, and block at high [CP] and [D]; more than 50% recovery is achieved by less than 1 min washout of CP and D. Currents carried by Na+ and Mg2+ ions behave similarly. It is concluded that activation of ACh evoked contractures may be blocked by CP independent of ionic currents through nicotinic ACh receptors and that it depends on intracellular processes linked to these receptors.