Temporal lobe epilepsy (TLE), the most common focal seizure disorder in adults, can be instigated in experimental animals by convulsant-induced status epilepticus (SE). Principal hippocampal neurons from SE-experienced epileptic male rats (post-SE neurons) display markedly augmented spike output compared with neurons from nonepileptic animals (non-SE neurons). This enhanced firing results from a cAMP-dependent protein kinase A-mediated inhibition of K Ca 3.1, a subclass of Ca 21gated K 1 channels generating the slow afterhyperpolarizing Ca 21 -gated K 1 current (I sAHP ). The inhibition of K Ca 3.1 in post-SE neurons leads to a marked reduction in amplitude of the I sAHP that evolves during repetitive firing, as well as in amplitude of the associated Ca 21 -dependent component of the slow afterhyperpolarization potential (K Ca -sAHP).Here we show that K Ca 3.1 inhibition in post-SE neurons is induced by corticotropin releasing factor (CRF) through its Type 1 receptor (CRF 1 R). Acute application of CRF 1 R antagonists restores K Ca 3.1 activity in post-SE neurons, normalizing K Ca -sAHP/I sAHP amplitudes and neuronal spike output, without affecting these variables in non-SE neurons. Moreover, pharmacological antagonism of CRF 1 Rs in vivo reduces the frequency of spontaneous recurrent seizures in post-SE chronically epileptic rats. These findings may provide a new vista for treating TLE.