1 The effects of propranolol, oxprenolol and practolol on the isometric twitch responses to electrical stimulation of isolated diaphragm muscles from the rat and of isolated papillary muscles from the rabbit are described.2 Depression of the twitch responses of the diaphragm muscle was produced by propranolol (20 mug/ml), by oxprenolol (100 mug/ml) and by practolol (500 mug/ml).3 Depression of the twitch responses of the papillary muscles was produced by propranolol (20 mug/ml) by oxprenolol (100 mug/ml) and by practolol (200 mug/ml).4 No increase of twitch tension was produced by oxprenolol or practolol on either tissue.5 It is concluded that propranolol, oxprenolol and practolol produce negative inotropic actions on isolated cardiac muscle by a mechanism unrelated to blockade of beta-adrenoceptors and which occurs at doses which are well in excess of those doses required to produce beta-blockade.