Previous findings on changes in K+-induced GABA release from hippocampal slices during kindling epileptogenesis were reinvestigated using physiological electrical stimulation. For that purpose, a procedure was developed enabling neurochemical monitoring of GABA release locally in the CA1 region of rat hippocampal slices upon tetanic stimulation of Schaffer-collateral fibers. In the presence of a GABA reuptake blocker, subsequent application of short (3 s) pulses of 50-Hz stimuli induced a local transient increase in GABA release. In slices from fully kindled animals, 24 h after the last generalized seizure, tetanically stimulated GABA release was increased in comparison to control slices. In slices from long-term kindled animals, 4-5 weeks after the last seizure, tetanically stimulated GABA release had returned to control levels. Application of the broad low-affinity GABAB receptor antagonist saclofen increased the tetanically stimulated GABA release in control slices, but had no effect in fully kindled slices. In slices from long-term kindled animals, however, saclofen enhanced GABA release similarly as in control slices. We conclude that the transient increase in tetanus-induced GABA release during kindling epileptogenesis is seizure-related, and probably caused by temporarily impaired presynaptic GABAB receptors. The possible relevance of this finding for GABA transmission in epilepsy is discussed.