It has been suggested that certain diseases of Man are caused by auto-antibodies, which develop because a tissue becomes auto-antigenic following alteration of the cells by toxins, chemicals or physical noxious agents or by intracellular parasites. In continuing the study of this possible role of auto-antibodies in the pathogenesis of disease, a study of the sensitization of red cells in various skin diseases was undertaken. The Coombs test for sensitization of red cells gave positive results in three of three cases of acute disseminated lupus erythematosus, in two of 14 cases of chronic discoid lupus erythematosus, in two of three cases of the Stevens-Johnson syndrome, in two of three cases of dermatomyositis, in one case each of scleroderma and Raynaud's disease, and in one case of erythema multiforme, which developed acute haemolytic anaemia. The cases in which the Coombs test gave a positive result were all relatively severely ill and the skin conditions could be regarded as only one of the manifestations of a generalized disease. In contrast, the cases with chronic benign conditions nearly all gave negative results. The findings suggest, but do not prove, that autoantibodies may play an important role in the pathogenesis of the conditions in which sensitization of the red cells was demonstrated. It is noted that most of these conditions are associated with a hyperglobinaemia, the significance of which needs further study. The indications for treatment of the auto-allergic diseases are discussed. It is noted that the inhibition of the inflammatory reactions associated with these conditions is of benefit to the patient. This can be achieved, temporarily, at least, in most cases by giving ACTH or Cortisone. On the other hand, the inhibition of inflammatory reactions in cases of infective disease is harmful and contra-indicated unless the infection can be controlled by drugs or antibiotics.