Clinical experience with radiosurgery for epilepsy on lesions located in highly functional areas has suggested the possibility of Gamma-Knife-induced functional effects without deterioration of the underlying cerebral cortex. To investigate these hypothetical functional changes, we have developed a special frame dedicated to small-animal radiosurgical experimental models, allowing purely atlasguided protocols. The left striatum of the first series of rats was targeted with high doses (200 Gy maximum) for validation of this new device. The same target was used with lower doses (50 Gy at the 50% isodose) in the second series to evaluate the biochemical changes and their chronology. The main biochemical changes occurred between 59 and 90 days after Gamma Knife irradiation, with different amplitudes depending on the biochemical parameter observed. Differential effects were first observed between glutamate decarboxylase and choline acetyltransferase, and secondarily between excitatory amino acids (AAs) and non-excitatory AAs, particularly gamma-aminobutyric acid. These preliminary results need to be confirmed and completed by further experimental studies. However, Gamma-Knife-induced differential biochemical effects provide the basis for a promising new concept for functional radiosurgery and particularly the Gamma Knife surgery of epilepsy.