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lesion is first macroscopically analyzable into zones which correspond 
with the microscopic findings, the growth of the lesion is seen to be due 
to a lateral extension of 3 elements. These may be described, from with- 
out inward, as— 
(1) A zone of hyperemia. 
(2) A vesicular ring, composed of— 
(a) A zone of translucence. 
(b) A zone of opacity. 
(3) A crust. 
Up to the end of the eighth day of the development of the lesion these 
move out from the line of inoculation in the order named, each encroach- 
ing upon its outer neighbor toward the end of this period, a little more 
rapidly than the latter spreads. On the eighth day of the development 
of the lesion this spreading stops, and the zone of hyperemia slowly 
fades, the opaque zone spreads over the remnant of the translucent zone, 
and it in turn is taken up by the spreading of the crust. 
The profile of the lesion presents 3 rather distinct phases, as follows: 
After 5 days it is more or less hemispherical, or at least an arc of a circle. 
After about 7 days it is flat-topped, presenting a steep declivity on either 
side, with perhaps a rampart effect from the depression of the crust, and 
after 8 days the whole lesion may be raised upon a broad swelling, which 
elevates with it some of the normal epithelium about it. 
(2) Histology of the vaccine lesion of the skin.—The histogenesis of 
the vaccine lesion in the skin of the monkey is similar to that of the vac- 
cine lesion in the skin of other mammals. We find the same changes in 
the epithelial cells leading to vesicle formation, followed by reparative 
processes resulting in complete healing of the lesion. The histology of 
the vaccine lesion has been described so often that it seems unnecessary 
to repeat it here. We find the development of the lesion to be the same 
after inoculation with different strains of virus. 
In the study of our large series of vaccinations of the monkey we have 
been struck by the extent of the process in the corium and in the subeu- 
taneous tissue beneath the lesion. We can recognize a general inflam- 
matory and reparative process, and besides a series of phenomena which 
we regard as due to the activities of the specific organism. The former 
group of phenomena are shown by cellular and fluid exudative processes 
and by proliferation of connective tissue cells with the new formation of 
blood vessels, and are such as would accompany any infected wound of 
the skin. Besides these we find early in the process a marked swelling 
and proliferation of the endothelial cells of the capillaries adjacent to the 
specific process in the epidermis. The endothelial cells of the capillaries 
and lymphatics in these situations are frequently invaded by the proto- 
plasmic phases of cytoryctes variole. This reaction in the corium is in 
evidence from the third day of the disease onward. We interpret. this 
condition as due both to the action of the toxines set free from the specific 
