We measured biochemical markers of excitability in brain excised for neurosurgical therapy of epilepsy. Intraoperative electrocorticography was used to identify and compare samples from regions of persistent interictal spike discharges and areas of the cerebral convexity which were free of interictal spiking. We found that interictal spiking was associated with elevated tissue levels of the excitatory amino acids glutamic acid (26%, p less than 0.001) and aspartic acid (25%, p less than 0.05). There was also a significant increase in the activity of the enzymes glutamic acid dehydrogenase (20%, p less than 0.01) and aspartate acid aminotransferase (18%, p less than 0.01) which are involved in their formation. There was no change in the levels of the inhibitory neurotransmitters GABA or taurine. We also found a significant increase in the activity of tyrosine hydroxylase (52%, p less than 0.001), the rate controlling enzyme in catecholamine biosynthesis. There was a reduction in the density (Bmax) of cortical alpha-1 adrenoceptors (26%, p less than 0.01) and a concomitant diminution of receptor coupled phosphatidylinositide metabolism (21%, p less than 0.01). This blunting of inhibitory noradrenergic transmembrane signaling may contribute to a relative imbalance between excitatory and inhibitory mechanisms in epileptogenic neocortex.