Temporal lobe epilepsy (TLE) is one of the most common, drug resistant forms of the syndrome. Many recent studies (including Shah et al. (2004)) have shown that following the induction of TLE the expression of the Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) subunits is reduced significantly in the dendrites of entorhinal cortical (EC) and hippocampal pyramidal cells. The significance of this, however, for the manifestation of TLE remains undetermined. To address this question, we have employed HCN1 null mice. Adult HCN1 null mice were more susceptible to kainic induced status epilepticus (KAS) than wildtype littermates. Following termination of KAS with an anticonvulsant, the mice also developed spontaneous behavioural seizures at a significantly more rapid rate than wildtype littermates. Cell-attached electrophysiological recordings from EC layer III dendrites present in entorhinal-hippocampal slices revealed that the hyperpolarization-activated cation current, Ih was ablated in HCN1-/- neurons. Although this resulted in neurones with more hyperpolarized resting membrane potentials (RMP), significantly greater numbers of action potentials could be recorded from the dendrites of these cells. This could be partly explained by the considerably augmented dendritic input resistance of HCN1-/- neurons. Consequentially, the integration of excitatory post-synaptic potentials (EPSPs) was significantly greater in HCN1-/- neurons such that at normal RMP, a 50 Hz train of EPSPs produced action potentials. On account of this pyramidal cell hyperexcitability, spontaneous EPSC frequency was considerably greater, causing an imbalance between normal excitatory and inhibitory synaptic activity. This altered neural neural network activity in the EC may, at least in part, explain the enhanced seizure susceptibility of the HCN1 null mice. Hence, dendritic HCN channels are likely to play a critical role in regulating cortical pyramidal cell excitability. Further, a decrease in expression of HCN subunits following the induction of epilepsy is likely to facilitate the disorder.