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1. Voltage clamp studies of the post-synaptic membrane of the insect neuromuscular junction have shown that normal amplitude glutamate currents could be recorded for a limited time when external Na was completely replaced by Ca, Li, ammonium, methylamine and guanidine. No change in the reversal potential of the glutamate current was observed when Na was replaced by these ions. It is suggested that the glutamate ionic channel has a similar permeability to Na and to these foreign cations, although the foreign ions cause a longer-term block of the permeability increase or receptor function. 2. Procaine, pentobarbitone, 2-4-6-triaminopyrimidine, high and low pH and low temperature reduced the synaptic ionic permeability but did not alter the ratio of the conductance increase of Na to K (delta g Na/delta gK). 4-Aminopyridine and TEA did not reduce the synaptic ionic permeability. 3. The 3. The properties of the synaptic ionic channels resemble the tight junction transepithelial ionic channels of the mammalian gall-bladder, but are very different from the Na and K non-synaptic channels of axons. It is suggested that Na and K normally pass through a single relatively large channel containing strong proton accepting acidic ligands which render the channel cation selective.