In patients with pharmacologically intractable epilepsy who are not eligible for surgery, deep brain stimulation is currently under evaluation as an alternative treatment. Optimal stimulation parameters, including high (HFS) versus low frequency (LFS) stimulation, are not well defined. Here, we report the effects of HFS (130 pulses per second, pps) and LFS (5pps) of the principal epileptogenic focus, in three patients with non-lesional temporal lobe epilepsy. HFS, but not LFS, was associated with a reduction of the interictal discharges and absence of seizures. HFS may be beneficial in patients with non-lesional temporal lobe epilepsy who are not surgical candidates.