Expression of hyperpolarization-activated, cyclic nucleotide-gated nonselective (HCN) channels has been described in many regions of the central nervous system. In the hippocampal formation expression of HCN channels are functionally relevant by determining resting membrane properties and regulating synaptic function. We therefore investigated the involvement of HCN channels in long-term potentiation (LTP) at synapses between medial perforant path (MPP) and granule cells of early postnatal and mature rats. In hippocampal slices from immature rats (P9-15) LTP was elicited by theta burst stimulation (TBS) resulting in a stable enhancement of field excitatory postsynaptic potentials (188 ± 23 %; n = 13) under control conditions. While application of the specific HCN channel blocker ZD7288 (10?µM) after TBS had no significant effect on expression of LTP (170 ± 13 %; n = 11) application before TBS constrained LTP (120 ± 8 %; n = 14). However, HCN channel inhibition by ZD7288 had no impact on LTP in slices of mature rats (P50-150), suggesting a pivotal role of HCN channels in the induction of LTP especially in the developing dentate gyrus. A significant reduction of LTP was also observed in HCN1-deficient, immature mice (172 ± 13 %; n = 13) as compared with wild types (283 ± 30 %; n = 7). These results demonstrate that HCN channels in immature, but not in adult MPP synapses are required for a normal magnitude of LTP. Moreover, HCN1 channels appear to contribute to HCN channel-dependent LTP induction.