*Meningitis.*--The intense headache, vertigo, delirium, and coma of meningitis, especially meningitis of the convexity without localizing symptoms, may be mistaken for severe prodromal symptoms of smallpox. As a rule, pulse and respiration are slow in meningitis, while in smallpox respiration and pulse are both markedly rapid. *Cerebro-spinal Meningitis.*--In cerebro-spinal meningitis, in which an erythematous or purpuric rash appears, the difficulties of diagnosis are often such as tax the skill of the most expert clinician. It is important to remember that the rash of cerebro-spinal meningitis usually develops gradually or in successive crops, and that its distribution over the cutaneous surface is irregular, while the eruption of smallpox makes its complete appearance within the space of a few hours and is localized chiefly on the face and extremities. The stiffness at the back of the neck and the retraction of the head are symptoms that do not belong to smallpox. *Septicæmia and Pyæmia.*--Acute septicæmic and pyæmic conditions in which there are hemorrhagic and bullous lesions in the skin sometimes present grave difficulties in making a differential diagnosis from smallpox. In general, however, a careful elucidation of the history of the case will bring out some points that serve for differentiation. It must be admitted, however, that the diagnosis between cryptogenetic septicæmia and hemorrhagic smallpox is sometimes impossible _intra vitam_. A case of this kind may be cited which occurred in New York during the epidemic last year. A woman of thirty, not vaccinated since childhood, living in a house adjoining one from which a case of smallpox had been removed, was reported to the authorities as a possible case of smallpox. It was the sixth day of her illness, which had begun abruptly with headache, backache, vomiting, and fever. On the third day of the illness there was a profuse hemorrhage from the uterus, and thereafter metrorrhagia was almost constant. On the fourth day a scarlatiniform eruption was noticed on the legs and abdomen. The rash rapidly extended and was soon interspersed with hemorrhagic points. When seen on the evening of the sixth day the patient was semi-comatose. The skin was literally covered with a dusky scarlet rash in which were noted countless hemorrhagic macules, from a pin-point to a bean in size. The conjunctivæ bulbi were chemotic, the tongue was swollen, and the fauces were deeply congested. The post-mortem examination made the following morning, six hours after death, revealed a septic endometritis, and streptococci were cultivated from the blood and the peritoneal serum.