Changes in the pH of interstitial fluid were measured with H+-selective double-barreled micropipette electrodes in fascia dentata of urethane-anesthetized rats. Paroxysmal afterdischarges provoked by repetitive stimulation of an afferent fiber tract brought in their wake acidification by 0.07 to 0.2 pH units. Spreading depression caused acidification by 0.2-0.5 pH units. Acid shifts were often preceded by transient alkalinization. Acidification is attributed to the production of CO2 and of other acid metabolites.