Interstitial thermotherapy using Nd:YAG-laser induced hyperthermia is a new stereotactic method for the treatment of brain tumors in poorly accessible regions. To provide a basis for the underlying tissue alterations, we have analyzed the spatial and temporal pattern of interstitial laser hyperthermia lesions in the normal rat brain by histological, immunohistochemical, and electron microscopical methods. The acute changes corresponded to the temperature gradient surrounding the laser probe and showed a distinct zonal architecture. Membrane destruction on a cellular and subcellular level appears to be of major significance in the pathogenesis of the laser lesion. The tissue reaction followed the course known for coagulation necrosis and resulted in a well-defined defect. These results, although limited by the choice of the experimental model, may be helpful in the interpretation of images obtained in future applications of interstitial thermotherapy.