There is probably no disease in regard to which our views have undergone so radical a change during the past few years as general paralysis of the insane, and none in which the discovery of the causative agent has been followed by so rapid a revolution in standpoint. Although almost from the time of its definition, more than a century ago, the essentially organic nature of the disease and its close relationship to syphilis have been universally recognized, it has required many years of patient study to free it from the hypotheses which have been invoked to explain its obscurities, and, as always happens in scientific progress, in the process of unravelling the knotty problems of this disease, we discover that there are new obstacles and difficulties to be overcome. Is the Spirochóte pallida alone responsible for the genesis of general paralysis? When does it gain access to the nervous system, and how? Is there a special strain of spirochóte, or must the individual resistance of the infected person be considered the deciding factor in the development of the disease? What is the meaning of the long latent interval before the onset of symptoms? What determines the peculiar distribution of the lesions in general paralysis, and is there some particular place in the brain from which the spirochæte starts its wandering? What is the significance of the absence of spirochætes in other organs of the body, and why does the cerebro-spinal fluid contain no organisms at a time when the brain contains millions? Why do tabes, general paralysis and optic atrophy, supposedly of similar origin, not occur in conjunction more frequently? Why is it that arsenical compounds fail to effect a cure?