Synaptically released Zn²⁺ is thought to modulate neurotransmission in the mammalian CNS by affecting currents mediated by postsynaptic neurotransmitter receptors. The inhibitory glycine receptor (GlyR) is potentiated by low micro molar concentrations of Zn²⁺ and inhibited at higher. Here, we examined the physiological relevance of Zn²⁺ neuromodulation in acutely isolated brain stem slice. We performed whole-cell voltage-clamp recordings in hypoglossal motoneurons from mice at postnatal day eight. It became obvious that endogenous Zn²⁺ enhances glycinergic IPSCs under resting conditions, since chelating Zn²⁺ by tricine reduces amplitude of IPSCs in hypoglossal motoneurons. This reduction of IPSC amplitude is partly missing in mice homozygous for mutation (Glra1(D80A)) involving the Zn²⁺ binding site of the glycine receptor a1-subunit. Our data indicated that modulation of glycinergic IPSC by Zn²⁺ is altered indication that Zn²⁺ modulation is essential for proper functioning of glycinergic neurotransmission. (Supported by DFG, CMPB).