Leuko-encephalopathy is a disease of the white matter of the brain occurring as a result of various exogenous and endogenous causes. It is one rare, but important cause being use of chemotherapeutic agents. Neurological manifestations are numerous with varying severity. Radiological features are characteristic of leukoencephalopathy well depicted on magnetic resonance imaging (MRI). Here the authors describe case of a gentleman with carcinoma rectum undergoing chemotherapy (5 fluorouracil and oxaliplatin) during which he developed severe encephalopathy with akinetic rigid state. MRI features were characteristic and there was complete clinical recovery and radiological resolution on stopping the causative agent.