Intracellular microelectrode recordings were made from presynaptic and postsynaptic regions of the third order giant synapses of the squids Alloteuthis subulata and Loligo vulgaris. Synaptically generated postsynaptic action potential trains, and excitatory postsynaptic potentials (EPSPs) were reversibly decreased by glycine, beta-alanine or taurine while presynaptic action potentials (APs) were unaltered. Glycine was effective in the presence of strychnine (30-50 muM), NMDA (500 muM), AP-5 (50 muM), CPP (100 muM), or MK 801 (which also had no effect on normal synaptic transmission). The glycine effect was reduced reversibly by D-tubocurarine (100 muM) and blocked by reducing extracellular chloride by 50% with propionate. Excitatory postsynaptic currents (EPSCs) were decreased by glycine addition without altering resting membrane conductance. We postulate that glycine or a glycine like substance provides an excitatory postsynaptic input during synaptic stimulation. Bath addition of glycine desensitises these receptors and decreases the amplitude of the EPSPs and EPSCs. Modulation of this synaptic input may provide an effective mechanism to suppress or potentiate synaptic transmission in the squid giant synapse. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.