Brief intracerebral injections of bicuculline in the anterior portion of the piriform cortex of the isolated guinea pig brain preparation induce a transient, localized disinhibition confined to the site of drug application. The epileptiform activity generated at the bicuculline focus propagates and induces secondary excitability changes in remote cortical regions within the olfactory lobe. Long lasting changes in synaptic potentials were observed in the posterior piriform cortex, where long-projective cortico-cortical fibers originating from the site of bicuculline injection terminate. The activation of rhythmic, transient afterdischarges at the bicuculline focus was critical for the development of persistent 'epileptiform' associative synaptic potentials in remote cortical regions. When transient afterdischarges were prevented, epileptiform associative potentials in the posterior piriform cortex appeared only transiently and vanished within 20 min. The persistent secondary changes in synaptic excitability that occur in cortical regions distant from the acutely-induced primary epileptic focus may represent one of the transition mechanisms toward chronic epileptogenesis.