One of the first advances which contributed materially to the ultimate solution of the general paresis problem was the study of the cerebrospinal fluid by Widal, Sicard and others after the introduction of lumbar puncture by Quincke in 1890. This led eventually to discoveries which were of great diagnostic importance. The isolation of the spirochaeta pallidum, now known as the treponema pallidum, by Schaudinn in 1905 settled the question for all time as to the cause of syphilis. The adaptation of the principle of complement fixation, the so-called Bordet-Gengon phenomenon, to the study of syphilitic fluids by Wassermann, Neisser and Bruck in 1906 practically removed all doubt as to the relation between that disease and general paresis. The demonstration of the treponema in the cortex of paretics by Moore and Noguchi in 1913 was practically the only other contribution necessary. They have since been found in the cerebrospinal fluid. Notwithstanding the fact that general paresis must now be looked upon as being a manifestation of syphilis beyond all peradventure of a doubt, it is nevertheless true that we are unable to explain why that disease does not always yield to specific treatment. This is undeniably the case at this time. Just why this should be so cannot be explained in the light of our present knowledge. It is, however, presumably for the same reason that tabes and other diseases of the cord and nervous system, the specific origin of which cannot logically be questioned, are equally resistant to salvarsan and mercury, whatever that reason may be. As soon as the findings of the Wassermann reaction became evident, renewed efforts on the part of clinicians to find a cure for general paresis naturally followed. One of the first suggested was the Swift-Ellis treatment. This was based on the injection of salvarsanized blood serum into the subdural space of the spinal canal. Results were exceedingly encouraging for a while, but time showed that this was not the solution of the problem. Intravenous salvarsan administration was next tried. This, too, gave excellent results at first. The cases which were apparently cured, however, eventually relapsed sooner or later in almost every instance. The intraspinous use of salvarsan in minute doses has been no more successful than the Swift-Ellis method. Intracranial subdural treatments have been tried and salvarsan has even been injected directly into the lateral ventricles. The logical conclusion is either that the destruction of the nervous tissue has already reached a stage which is beyond repair or that the treatment does not reach the site of the disease.