Intracellular pH (pHi) has been shown to suppress epileptic discharges in many animal hippocampal models. However, studies on the effect of pHi upon epileptic activity are missing in the human neocortical brain slice. Here we investigated the effect of 0-Mg plus elevated potassium (6–8 mM) treatment on epileptiform activity recorded intra-cellularly from human layer III-V neurons. pHi measurements of BCECF-AM loaded slices were carried out in the same regions in parallel. All slices were superfused with bicarbonate buffered saline. We found that application of 10 mM sodium propionate (n=5) reduced the intracellular pHi of the superficial fluorescent cells by less than 0.1 pH units. Lactate (10 mM) led to similar though attenuated changes of pHi. Changes in pHi seen upon propionate or lactate were partly regulated and showed a rebound alkalosis upon washout. Epileptiform discharges (ED, duration: 2–10s) were shortened and their frequency was reduced during intracellular acidosis (n=6). Alkalosis, in turn, prolonged EDs. Results suggest a pivotal role of pHi for an inhibition of human temporal lobe epilepsy. As neural excitability was influenced by lactate, substrates used for energy metabolism may influence excitability.