During the past few years, one of us (F. W. M.) has had exceptional opportunities of seeing patients suffering from various mental complaints, and of comparing the results of post-mortem examinations with the symptoms exhibited during life. One of the commonest complaints seen in the London County Asylums is General Paralysis of the Insane, and it was with a view of elucidating some of the pathological problems connected with this disease that the present enquiry was originally undertaken. How far this object has been attained will be discussed at the conclusion of the paper. The disease is one which is characterised by an extensive degenerative and wasting process occurring in the cerebral cortex, especially in the frontal and central convolutions ; during the course of the disease there are frequent seizures of a congestive, epileptiform or apoplectiform kind, and after the recovery of the patient from each of these fits, he is, as a rule, worse mentally. Each fit probably indicates the breakdown of a new focus of cerebral matter. The disease is a premature, primary, progressive decay of the neuron affecting especially those structures which have been developed latest. It is a para-syphilitic affection like tabes, with which it is, pathologically speaking, identical.