Morphological, histopathological, and immunological studies of seven strains of rickettsial disease have placed them in two widely separated groups, for which typhus and spotted fever seem the most logical names.

Diseases of the spotted fever group are carried by ticks (Arachnoidea) and characterised by distinctive histopathological lesions—thrombonecrosis of arterioles and venules, with micro-organisms of definite and characteristic morphology, invading smooth muscle cells, as well as endothelium, mesothelium, and macrophages. Tissue culture studies show massive invasion and distention of cell nuclei, while cytoplasmic invasion of host cells is relatively sparse.

Diseases of the typhus group are carried by lice and fleas (Insecta) and characterised by the facts that the intracellular parasite which causes them invades only endothelium and mesothelium, distends the cytoplasm of its host cells without ever invading nuclei, and in guinea pigs causes only proliferative endangeitis without thrombonecrosis.

In the spotted fever tick, organisms are intranuclear as well as intracytoplasmic, invade nearly all types of tissue, and are transmitted hereditarily. In typhus-infected lice and fleas, organisms are intracytoplasmic only, infect only the lining cells of the gut, and are not transmitted hereditarily.

Neither focal brain lesions nor scrotal sac exudation is of importance in the differential diagnosis, since both occur in certain strains of spotted fever, as well as in typhus. Definite necrosis of the scrotum is of importance, since it is dependent upon the above-described arteriolar thrombonecrosis and is peculiar to spotted fever.

A review of the literature shows that rickettsial diseases and their etiological agents are being classified in an inaccurate and unjustifiably complex manner, specific names often being given to organisms without the presentation of evidence sufficient to establish them as new varieties.

A plea is made for the study of unclassified or unsatisfactorily classified diseases in all parts of the world by the methods described, and for their classification on the basis of morphologic and histopathologic observations on insect and mammalian hosts and of immunological studies on the latter, rather than on variations in clinical pictures in man and in experimental animals.

The criteria for the differential diagnosis between typhus and spotted fever are presented in tabular form and illustrated wherever possible. All reported rickettsial diseases as well as their etiological agents are classed on the basis of the criteria presented, and, with the exception of the incompletely studied mite-borne group, the available evidence strongly suggests that all are varieties of typhus and spotted fever.

The morphological, histopathological, and immunological differences between typhus and spotted fever are so great that these two diseases, as well as their causative organisms, should be widely separated from one another, and given definitely distinguishing names.

It is suggested that the well-established name, Rickettsia prowazeki, be applied to intracytoplasmic micro-organisms in Insecta causing all diseases of the typhus group, and that Dermacentroxenus rickettsi (the name originally given by Wolbach) be applied to hereditarily transmitted micro-organisms invading nuclei in Arachnoidea and in tissue cultures, causing all diseases of the spotted fever group. Specific varieties, when established by the demonstration of definite and constant biological differences, should be indicated by variety names, as Rickettsia prowazeki mooseri (for endemic flea-borne typhus in all parts of the world).