of Tatarstan, U.S.S.R.1 Acetylcholine (ACh), 7.5 x 10-5M, and carbachol, 5 x 10-6M (CCh) depressed the frequency of miniature endplate potentials (m.e.p.ps) in the frog (Rana temporaria) sartorious neuromuscular junction with active acetylcholinesterase to about 50-55% of the controls. 2 A similar depression was produced by the nicotinic agonists, nicotine, suberyldicholine and tetramethylammonium. 3 The muscarinic agonists, oxotremorine, methylfurmethide and methacholine were without effect on m.e.p.p. frequency. The muscarinic antagonist, atropine and the nicotinic antagonist, (+)-tubocurarine, had no effect on the depression of m.e.p.p. frequency evoked by CCh. 4 The ganglionic blockers, benzhexonium and IEM-1119, were also without effect on the CCh-evoked depression of m.e.p.p. frequency. 5 Pretreatment of muscles with anticholinesterases did not prevent the CCh-induced drop in m.e.p.p. frequency. 6 The effect of CCh was proportionally the same as in the controls in preparations where the m.e.p.p. frequency was changed by elevation of K+ and in the presence of theophylline, noradrenaline, dibutyryl adenosine 3': 5'-cyclic monophosphate (db cyclic AMP) and db cyclic GMP.7 An inhibitor of Na+,K+-ATPase, ouabain, 5 x 10-5mollP', prevented or reversed the depression of m.e.p.p. frequency by CCh. However, the depression was present in a nominally K+-free medium. Insulin and adrenaline, which are considered to be Na+,K+-ATPase activators, were without effect on depression of m.e.p.p. frequency. 8 The depression of m.e.p.p. frequency by 5 x 10-6 M CCh was the same at temperatures between 5 and 30°C with a Q10 near to 1.0. When threshold amounts of CCh were used (6 x 10-7 and 3 x 10-7 M), the depression was less at higher temperatures. 9 The receptive structures responsible for the CCh (or ACh)-evoked depression of m.e.p.p. frequency differ pharmacologically from muscarinic, nicotinic ganglionic and neuromuscular junction ACh-receptors as well as from the synaptic cholinesterase, in contrast to previous reports (Duncan & Publicover, 1979). The low temperature-dependence points to the possibility that physical rather than biochemical processes are limiting in this presynaptic effect of cholinomimetics.