Neurochemical observations on cortical biopsies form 48 patients under surgical treatment for pharmacoresistant partial epilepsy showed a 70-80% increase in glutamate concentration when expressed in relation to neuron specific enolase. Intraperitoneal administration of one of its receptor agonists, kainic acid (KA), to the rat led to increased epileptogenic activity of the limbic type in a dose-dependent fashion. The KA injection also led to a neuronal cell death and a gliosis, closely correlated to the extent of seizure activity. In biopsies from human epileptogenic cortex, the concentration of neuron specific enolase correlated inversely to that of glial fibrillary acidic protein, a marker for astrocytic glial cells. Stimulation of the KA receptor decreased the extent of phosphorylation of the largest subunit of neurofilaments (NF-H) that have consequences for structural stability and axonal transport. Phosphorylated NF-H decreased also in human epileptic cortex, indicating either an overactivity of excitatory neurotransmitters or a loss of axonal compartments.