In the presence of 4-aminopyridine and excitatory amino acid receptor antagonists, individual neurons in brain slice preparations exhibit large gamma aminobutyric acid (GABA)-mediated responses as a consequence of synchronous GABA release from a network of interneurons. These synchronized GABA responses are frequently associated with ectopic action potentials (EAPs), which are thought to be action potentials initiated in distal axon terminals which subsequently travel antidromically toward the soma. Ectopic action potentials feature prominently in some models of epilepsy. Neocortical synchronized GABA responses propagate across the cortex, predominantly in superficial layers. The role that EAPs may play in contributing to laminar differences in the synchronized GABA response has not been addressed. Here we examined the occurrence of EAPs during synchronized GABA responses in neurons within layers I and II/III. EAPs occurred in 78% of layer I interneurons and in 25% of layer II/III interneurons (including chandelier cells). EAPs were not observed in layer II/III pyramidal neurons. The prevalence of EAPs in layer I interneurons provides a mechanism by which layer I can support both the initiation and propagation of synchronized GABA responses. Thus, layer I interneurons are a critical component of a network capable of synchronizing a propagating wave of GABA release across the neocortex. © 2005 Published by Elsevier Ltd on behalf of IBRO.