Using low frequency (quenching) stimulation parameters (1 Hz for 15 min), similar to those that induce long-term depression (LTD) in vitro, we attempted to alter amygdala kindling in vivo in rats. Quenching completely blocked the development and progression of after-discharges and seizures in seven of eight animals. In fully kindled animals, once-daily quenching stimulation for one week (without concurrent kindling) suppressed the seizures when kindling stimulation was resumed. These effects of quenching probably resulted from the marked and long-lasting increases in the afterdischarge and seizure thresholds that were observed in these animals. These data indicate that quenching with low frequency electrical stimulation (which does not disrupt ongoing behavior) can have profound and long-lasting effects on seizure development, expression, and thresholds. The ultimate clinical applicability of low frequency stimulation in the treatment of seizures and related neuropsychiatric disorders remains to be explored.