Significance Whereas glycine is one of the three major neurotransmitters in the central nervous system, glycinergic synapses are relatively understudied in intact tissue. Here we provide the first evidence of long-term potentiation (LTP) at mammalian glycinergic synapses. In the spinal cord dorsal horn, glycinergic synapses on inhibitory GABAergic neurons exhibit LTP, occurring rapidly after exposure to the inflammatory cytokine interleukin-1 beta. This form of LTP is mediated by postsynaptic alterations in glycine receptor function. We further show that peripheral inflammation in vivo triggers glycine receptor LTP. Blocking glycine receptor LTP may represent a useful therapeutic strategy in the treatment of inflammatory pain.