1 The effects of nicotine antagonists on single twitches, trains of four twitches and tetanic contractions of the isolated diaphragm of the rat were examined. 2 Different drugs were found to produce different amounts of tetanic fade relative to depression of twitch tension. 3 The order of activity from most able, to least able to produce fade was: hexamethonium>trimeta-phan = atracurium = tubocurarine > pancuronium > erabutoxin b. 4 The effect of erabutoxin b was distinctive for its almost complete lack of tetanic fade. 5 3, 4-Diaminopyridine increased tetanic fade produced by tubocurarine, atracurium and hexamethonium, but not that produced by erabutoxin b. 6 It is concluded that nicotinic antagonists act at more than one site at the neuromuscular junction. Assuming block of the postjunctional acetylcholine receptor produces tension depression, a second or third site must be involved in producing tetanic fade. 7 The possibility that tetanic fade results from block of the ion channel associated with the postjunctional acetycholine receptor or from the block of a prejunctional nicotinic receptor is discussed.