Cell-to-cell communication in the mammalian nervous system does not solely involve direct synaptic transmission. There is considerable evidence for a type of communication between neurons through chemical means that lies somewhere between the rapid synaptic information transfer and the relatively non-specific neuroendocrine secretion. Here I review some of the experimental evidence accumulated for the GABA system indicating that GABA(A) receptor-gated Cl-channels localized at synapses differ significantly from those found extrasynaptically. These two types of GABA(A) receptor are involved in generating distinctly different conductances. Thus, the development and search for pharmacological agents specifically aimed at selectively altering synaptic and extrasynaptic GABA(A) conductances is within reach, and is expected to provide novel insights into the regulation of neuronal excitability.