SUMMARY AND CONCLUSIONS. 
Normal horse serum, when injected into the peritoneal cavity of a 
normal guinea pig. produces no symptoms. When injected subcuta- 
neously there may result at most a slight local reaction consisting of 
swelling and edema, which gradually disappears. 
Antitoxic horse serum is equally harmless for normal guinea pigs. 
Horse serum is, however, poisonous to a guinea pig which has pre- 
viously been injected with horse serum. Tne “ period of incubation” 
or time necessary to elapse between the first and second injection is 
about ten days. Under these circumstances, horse serum is poison- 
ous whether injected subcutaneously or into the peritoneal cavity. 
The first injection of horse serum renders the guinea pig susceptible. 
The symptoms caused by the injection of horse serum into a sus- 
ceptible guinea pig are respiratory embarrassment, paralysis, and con- 
vulsions, followed by death. The symptoms come on usually within 
ten minutes after the injection, and when death results it usually 
occurs within one hour, frequently in less than thirty minutes, and 
sometimes within a few minutes. 
The poisonous . principle in horse serum appears to act upon the 
respiratory centers. The heart continues to beat long after respira- 
tion ceases. 
The toxic action of horse serum bears no relation to diphtheria. 
The poison is not toxone. Guinea pigs can not be rendered suscep- 
tible by previous infections with the B. di'phtherix or by previous 
injections with diphtheria toxine. 
It seems from our work, however, that guinea pigs first injected 
with a mixture of diphtheria toxine plus horse serum are more sen- 
sitive to subsequent injections of horse serum than are guinea pigs 
sensitized with a first injection of horse serum alone. 
Diphtheria antitoxin plays no part in this poisonous action 
AND IN ITSELF IS HARMLESS. 
As soon as we realized that the toxic principle in horse serum 
exerts its action in quantities so minute as to place it almost in the 
category of the ferments and, further, when we concluded from 
our work that this toxic principle is doubtless one of those highly 
organized and complex proteid substances belonging to the “haptin 
group” in the sense used by Ehrlich, w^e recognized how 7 futile it 
would be with present methods to attempt to isolate this substance. 
( 91 ) 
