The presence of the excitotoxic and convulsant agent quinolinic acid (QUIN) in human brain has led to the hypothesis that an increase of this tryptophan metabolite could serve as an endogenous epileptogen. A possible mechanism for a pathological accumulation of QUIN being a deficiency in its degradation, we have measured the activity of quinolinic-phosphoribosyl transferase (QPRTase) (its first degradative enzyme) in stereo-EEG identified biopsies of human brain tissue. A specific reduction of QPRTase activity was observed in tissue primarily involved in the epileptic discharge compared to values from postmortem human brain tissue with no neurological disorders or nonpathological tissue from epileptic brains. A more severe decrease was noticed in the frontal and temporal cortices as compared to the amygdala or Ammon's horn. We suggest that this local deficit may contribute to the establishment or maintenance of an epileptic focus.