The vesicle is divided irregularly by little bands, or septa, which permit only a portion of the fluid to escape when one is punctured. Vesiculation is usually complete about the third day, and the stage generally lasts three days. It may be stated here that the reckoning in smallpox is usually from the appearance of the rash. The period of incubation and invasion are considered in reckoning the length of illness, but in descriptions of smallpox it is considered best to state the day of the eruption, and not of the disease. There is an old and oft-repeated statement that a uniform rash is a characteristic of smallpox and that a mixed rash indicates chicken-pox. This deserves to be promptly refuted. It is most unusual to find a case of smallpox with its eruption all in one stage. While it is a well known fact that chicken-pox runs a hasty course,--so that in from one to two days we may have macules, papules, vesicles, and even crusts,--in smallpox this is not likely to occur, as the disease never runs such a rapid course. In the early stage we may see macules changing into papules on the head and the neck, while there are simply macules on the trunk. Later in the disease the eruption may be vesicular on the head while still papular on the body. When vesiculation is complete, we have the distinct umbilicated appearance that has long been recognized as a characteristic of smallpox. The vesicles are broad, firm, flat, and hard, and are invariably indented or umbilicated. It is not until the stage of vesiculation that the constitutional symptoms diminish to a marked degree. In fact it is considered one of the landmarks of the disease for the fever curve to show a decline at this time. Late in the fifth or early in the sixth day the vesicle begins to assume a cloudy or yellowish hue, which denotes the commencement of pustulation. The fluid continues to grow more yellow, and about the time that it has assumed a dense straw color the umbilication begins to disappear, so that in from one to three days the pustule loses its indented appearance and becomes globular in form. To the touch it appears to involve as much of the skin below the surface as it is high above it. It is during the stage of pustulation that the surrounding skin becomes swollen and œdematous, with an area of redness about the pustules giving the appearance of a bull’s eye. It is also during the pustular stage that the constitutional symptoms become more intense and the fever rises in proportion to the severity of the attack. The pustules are fully matured about the eighth day of the eruption. During the pustular stage the affection of the mucous membranes reaches its height. The eyelids, lips, and nose are often tremendously swollen. The tongue swells and deglutition becomes impossible. The voice is husky, and is sometimes lost, owing to the swelling of the glottis.