A clinico- anatomical study, from the developmental aspect, of three cases of subacute diffuse cerebral solerosis,with a note about the demyelinating diseases generally, the developmental nervous disorders and the functional psychoses. In an introduction, attention was drawn to the special vulnerability of the tissues of bodily organs curing the morphogenetic phase of their development, to the specially prolonged morphogenesis of the nervous system and, in particular, to the continued morphogenesis of the cortical mantle of the human brain r ight up to full adult life. The extent of present ignorance, however, about the role in disease of late maturational processes in the human brain was emphasised, together with the importance of this topic for an adequate understanding not only of the so- call: :ed developmental nervous disorders of post natal life but of the more urgent problem of the functional psychoses. It was pointed out that, while further advances could be expected in the field of post natal cerebral histogenesis and the corresponding field of behavioural developments advances in the neuropathology of these conditions, which rarely come to autopsy, would probably be delayed. In the light of these observations the unique importance was emphasised of careful clinical and pathological studies, from an earlier stage than heretofore, of the rarer, more serious, diffusely acting, diseases of the still maturing brain. A clinical and pathological study, from the developmental aspect, of three cases of subacute diffuse sclerosis of the brain, occurring at widely different ages and studied clinically from an nnn,sually early stage, was offered as a contribution to this problem. In this study, an outline was first given of present knowledge about postnatal growth and maturation of the human brain during infancy, childhood and adolescence and of the behavioural development which it subserveswith special reference to the maturation of the cerebral white matter and its oligodendroglia. This was followed by full clinical and pathological accounts of the three original cases of subacute diffuse sclerosis. Then, in the light of the actual findings, the role of a developmental, myelinogenetic, tissue factor in subacute diffuse sclerosis was discussed and certain general conclusions drawn. In this discussion, a historical survey first outlined the development of interest in diffuse sclerosis and in particular drew attention to references in the literature which could be interpreted as suggesting that the onset of the disease might have a relationship to some terminal and peculiarly vulnerable stage in the maturation of myelin in the brain. Then, from the clinical aspect, it was pointed out that early symptoms though variable and inadequately studied, seemed to have a certain specificity for age of onset and that, more particularly, in the three cases described, it had been deterioration of the behavioural characteristic of the individual most actively maturing at the time which had constituted the initial disturbance. In the infant this had taken the form of a progressive failure, from the age of nine months, to learn to stand erect and to walk unaided, in the yalung schoolboy it had taken the form of a failure, from the age of six years, to complete the process of learning to read and in the case of the adolescent it had taken the form of failure, from the age of thirteen or fourteen years, to complete the emotional, intellectual and social maturation characteristic of that epoch. From the pathological aspect, the actual findings were found to be consistent with, and in certain particulars to confirm,in the light of present knowledge of the anatomical basis of these capacities, anatomical deductions from the clinical observations. From the aetiological aspect, little light was thrown upon specific cerebro- exogenous, genetic or constitutional tissue factors in the particular cases and, with regard to the possibility of a developmental tissue factor, the inadmissibility of drawing definite conclusions from the findings in only three cases was acknowledged. However, the rarity of diffuse sclerosis, and still more of its detailed clinical study from an early stage in patients of widely different ages, was pleaded as a valid reason for the argument that the findings suggested, and certainly were consistent with, the tentative hypothesis that the initial demyelination had taken place in regions of the white matter where some terminal phase in myelin maturation, possibly related to the metabolism of the neurokeratin proteolipids, had been most actively taking place. Certain even more tentative suggestions were finally put forward about an analogous developmental tissue factor in the demyelinating diseases generally, particularly in the concentric sclerosis of Balo and in multiple sclerosis. In particular, it was suggested that the hitherto unexplained tendency, in multiple sclerosis, to the formation of symmetrical lesions, could be explained on the basis of such a factor. Finally, there was brief reference to possible histogenetic factors in the develop: :mental nervous disorders, especially specific developmental dyslexia, and in the functional psychoses, particularly schizophrenia.