The more modern and advanced opinion of the present day, not of necessity the most correct, regards toxic action as the most important factor in the pathogenesis of insanity. According to this view insanity is not regarded as primary disease of the brain, but secondary, and due to toxins derived from elsewhere acting upon the cortical nerve-cells, disordering their metabolism, and thus affecting their functional activity, damaging, or destroying them. The older psychologists are evidently disinclined to accept the toxic theories of the younger school, and cling with pertinacity to their opinion that mental disease is as a rule primary, and that the physical manifestations of ill-health result from a disordered central nervous system, and undoubtedly many of the facts they produce in support of their argument are difficult to refute; on the other hand, it is necessary for those who advance the theory of toxaemia as the essential factor in the production of insanity to marshal facts supporting their contention. By the term “auto-intoxication” we indicate toxins evoked within the body as a result of disordered metabolism, first, such as takes place in chronic Bright's disease, myxcedema, diabetes, etc.; and secondly, in the contents of the gastro-intestinal tract. Within the limits of this paper I propose only to deal with the second division, viz, auto-intoxication from the gastro-intestinal canal, for the cases coming under this group are by far the more numerous and important. For a long time I have strongly held the opinion, as a result of my own observations, that a very large proportion of cases suffering from melancholia are due to auto-intoxication resulting from the absorption of toxins from the alimentary tract, for in depressed states generally there are various symptoms referable to disordered metabolic processes in some part of the gastro-intestinal tract. The symptoms in question that I consider as evidence of a state of toxaemia are as follow: foul breath, coated tongue, indifference to and often refusal of food, marked constipation, foul stools, anaemia (varying in degree), a sallow dirty skin, profuse perspirations and of offensive odour, skin irritations, eruptions, disorders of sensation, often leading to flesh-picking, and headache. Of course we do not in any one case find all these symptoms, but there are several common to all cases of acute melancholia. It may be suggested that the signs and symptoms that I have mentioned as those of toxaemia are but those of lowered general health, and do not in themselves afford any direct evidence of the absorption of toxins, but I have observed that the signs and symptoms that I refer to as constituting toxaemia so commonly present in states of mental depression are constantly associated with the presence in the urine of indoxyl, in greater or lesser excess.