Tetanus toxin is a potent neurotoxin that is widely considered to produce its effect through impairment of inhibitory neurotransmission. We report the effect of a single unilateral intrahippocampal injection of tetanus toxin on extracellular levels of neuroactive amino acids in freely moving rats, at times ranging between 1 and 7 days posttreatment. Tetanus toxin treatment did not alter extracellular levels of aspartate, glutamate, and taurine at any time during the study. However, although extracellular GABA levels were unaffected by toxin injection 1, 2, and 3 days after treatment, they were reduced (45 +/- 8% of contralateral vehicle-injected level) at day 7. Challenge with a high K+ concentration, 7 days after treatment, produced elevations in extracellular levels of taurine and GABA in both vehicle- and toxin-injected hippocampi, with evoked levels of GABA being lower in the toxin-treated side (39 +/- 16% of contralateral vehicle-injected level). Aspartate and glutamate levels were not increased by high-K+ infusion. These findings are discussed in relation to the possible role that an imbalance in excitatory/inhibitory tone may play in the production of tetanus toxin-induced neurodegeneration.