The clinical application of enzyme estimations in the cerebrospinal fluid (CSF) is reviewed. Relevant features of the physiology of the CSF in man, the precautions needed to obtain representative samples and valid controls, and the sources of enzyme in CSF are considered. Brief reference is made to the application of CSF enzyme assays in cerebrovascular disease and tumour diagnosis and in other neurological conditions including head injury and cerebral anoxia. Although at least 30 enzymes have been demonstrated in the CSF of man only glutamic-oxaloacetic transaminase (GOn and lactate dehydrogenase (LDH) have received much clinical attention. Lesser studies have been made on phosphohexose isomerase, isocitric dehydrogenase, phosphatases, ,B-glucuronidase, aldolase and creatine kinase. No comprehensive review has appeared in recent years. Green (1958) gives a fairly full account of papers up to that date and a few more recent works are quoted by Plum (1964). A review is in preparation for publication from this department. Attempts have been made to apply CSF enzyme estimations: (1) in cerebrovascular disease, to assess the presence, extent and progression of infarction and in efforts to distinguish thrombosis from haemorrhage, (2) to cerebral tumour suspects, as an aid to diagnosis and to differentiation of benign from malignant growths and tumours from infarcts, and to detect recurrence, (3) in cases of head injury, to assess severity and guide prognosis, and (4) in the assessment of perinatal hypoxia. In meningitis there is increased activity of several enzymes in CSF: correlation with the different types of meningitis has not been fully investigated. Enzyme changes have been reported in the CSF from cases of demyelinating diseases but no recent studies seem to have been made here. Sources of enzymes in the CSF are: (1) from the blood plasma via the choroid plexus, (2) from addition of whole blood in trauma and strokes and, more rarely, by haemorrhage into tumours and from bleeding secondary to coagulation defects, (3) from excess of white blood cells in meningitis and leucaemia, (4) from normal brain damaged by infarction, external trauma and internal compression, or rendered transiently more permeable by hypoxia