In response to orthodromic stimulation, granule neurons of the dentate gyrus of the rat hippocampal slice display a late hyperpolarization (LH) with properties which clearly distinguish it from the conventional gamma-aminobutyric ac id (GABA)-mediated chloride (Cl) dependent inhibitory postsynaptic potential (IPSP). The LH is not reduced by antagonists of GABA-mediated Cl conductances such as picrotoxin, and it is probably dependent on increased potassium conductance rather than in increased Cl conductance. The LH can be elicited by orthodromic stimulation which does not elicit a burst of action potentials and, in fact, the LH has been observed following stimulation which did not produce a depolarization detectable at the resting membrane potential. It is suggested that the increased potassium conductance of the LH may be calcium-dependent, or it may be directly elicited by a neurotransmitter.