Activity-induced long-term modification of glutamatergic synapses depends on the frequency of synaptic activation. Here we report that long-term modification of developing rat hippocampal GABAergic synapses induced by repetitive coincident pre- and postsynaptic spiking is also frequency-dependent. Spiking at 20-50 Hz resulted in synaptic potentiation, whereas spiking at 5 Hz led to synaptic depression. The potentiation was abolished by blocking GABAB receptors (GABABRs), whereas the depression was independent of GABABR activation and could be converted to potentiation by elevating GABABR activity. The potentiation could be attributed to a local postsynaptic increase in Na+/K+/2Cl- cotransporter activity near activated synapses. The activity of postsynaptic Ca2+/calmodulin-dependent protein kinase II was necessary for LTP of these developing GABAergic synapses and its phosphorylation at Thr286 could be enhanced by activating GABABRs with baclofen. Together with the finding of frequency-dependent activation of GABABRs, these results indicate that postsynaptic GABABR activation mediates frequency-dependent potentiation of developing GABAergic synapses.