A light-fixed and dilated pupil is considered an iconic sign in acute neurology and neurosurgery, and has been considered a grave sign. Its significance was not known before the 19th century. Although changes in pupils in moribund patients have been known since antiquity, laboratory studies that focused on measurements of the consequences of acute mass effect in the brain provided the first pieces of information that led to a better understanding of its pathophysiological meaning.At some point in time, laboratory observations translated to clinical practice, but authors already often combined laboratory study results with clinical case observations. One of the first clinical articles was by surgeons Holman and Scott, who emphasized that surgery should be on the side of the dilated pupil. 25 Pupil dilation became recognized in the deteriorating patient often coinciding with decorticate or decerebrate responses indicating acute brainstem injury. Currently the pathophysiology is poorly The aim of this study was to investigate the development of ideas about the nature and mechanism of the fixed dilated pupil, paying particular attention to experimental conditions and clinical observations in the 19th century. Starting from Kocher's standard review in 1901, the authors studied German, English, and French texts for historical information. Medical and neurological textbooks from the 19th and 20th centuries were reviewed to investigate when and how this information percolated through neurological and neurosurgical practices. Cooper experimented with intracranial pressure (ICP) in a dog in the 1830s, but did not mention the pupils. He described dilated pupils in clinical cases without referring to the effect of light. Bright demonstrated to have some knowledge of the pupil sign (clinical observations). Realizing the unreliability of the pupil sign, Hutchinson in 1867-1868 tried to reason in which cases trepanation would be advisable. Von Leyden's 1866 animal experiments, in which he increased CSF volume by injecting protein solutions intracranially, was the first observation in which the association between fixed dilated pupils and increased ICP was established. Along with bradycardia and motor and respiratory effects, he noticed wide pupils were usually present in a comatose state. Asymmetrical dilation could not always be attributed to increased ICP, but to an oculomotor nerve lesion. Pagenstecher in 1871 extended knowledge by meticulously studying consecutive pupil phenomena with increasing pressure. In 1880, von Bergmann emphasized the significance of the ipsilateral dilation in experiments as well as in clinical cases. He distinguished the extent of pressure increase and its duration. Probably confusing irritation (epileptic head turning to the other side with pupil dilation) and lesion effects, he suggested a cortical area responsible for oculomotor phenomena, indicating what is now known as the frontal eye field. Naunyn and Schreiber (1881) understood the relationship between increased ICP with pupil dilation and ...