Radiation myelopathy is a rare, but highly feared complication of radiotherapy. In vivo characterization of radiation induced pathological processes by functional imaging methods has only recently become possible, most promisingly by positron emission tomography (PET). Although data about the pathomorphology of radiation related damage abound, previous PET studies have provided only limited information on the radiation-induced reactions of the central nervous system (CNS). Data on spinal cord damage are practically not available, since the reported investigations focus exclusively on the pathological changes of the brain, most probably because of the low spatial resolution of PET cameras. We have carried out PET studies on a total of 5 patients suffering from different forms of radiation induced damage of the spinal cord in order to complete the information having been obtained by conventional imaging and non-imaging diagnostic methods. One patient represents a case with complete recovery of the spinal cord following a subthreshold dose of irradiation. Two nasopharyngeal cancer patients were investigated due to permanent Lhermitte’s sign after radiotherapy. We have reported on PET findings in a patient with partially reversible radiation myelopathy, which were later correlated with autopsy results after her demise. A patient with radiogenic lower motor neuron disease was also investigated by PET. All patients exhibited increased FDG accumulation indicating elevated levels of glucose metabolism in those spinal cord segments that had been included in the radiation fields. Regional tissue perfusion measurements with [15O]butanol showed parallel results, excluding severe deterioration of microcirculation. The increased tracer uptake observed can properly be attributed to a higher energy demand, since glucose is the primary fuel to nervous tissue. The need of this extra energy could not be attributed to cell proliferation on the basis of either the anamnestic data or the pathologic findings, and was further supported by the results of [11C]methionine PET measurements. The restoration of axonal conduction, reflected by the improvement of the clinical symptoms, suggests that an alternative conduction mechanism (continuous impulse propagation) takes place in order to overcome the blockade caused by the loss of myelin sheath. This implies an elevated number of Na+-channels resulting in more effective Na+/K+-pump function, hence higher ATP demand.