INTRODUCTION 29 



injection ot the same filtrate. Four hours after the intravenous 

 injection there appeared severe hemorrhagic necrosis at the pre- 

 pared skin site. In the gross it was dark blue, swollen, ^vith an 

 angry red periphery and histologically it showed disruption of the 

 venules, extensive hemorrhage, thrombosis and necrobiosis of all 

 the cells. The reaction extended from the superficial layers of 

 the skin through the entire thickness of the abdominal wall to the 

 peri tone inn. 



For the reproduction of this phenomenon it is essential to gi\'e 

 the second injection into the blood stream. Repeated skin injec- 

 tions of the filtrate with twenty-four hour interval between injec- 

 tions does not result in the hemorrhagic and necrotic type of 

 reaction of the phenomenon. 



The phenomenon can be also produced ^vhen the skin prepara- 

 tion ^vith a given bacterial filtrate is followed by the intravenous 

 injection of filtrates derived from biologically and serologically 

 unrelated microorganisms. 



A definite interval of time is required bet^veen the preparatory 

 skin injection and the intravenous injection of the filtrate. A t^vo 

 hoiu' interval is insufficient. The state of reactixity appears as 

 early as eight hoins after the skin-preparatory injection and with 

 the filtrates employed in the basic experiments, does not last 

 longer than thirty-t^vo hours. The optimimi incubation period 

 is twenty-foiu' hoins. 



Primary reactions obtained upon intradermal injections of bac- 

 terial filtrates employed in this work are sharply contrasted by 

 the hemorrhagic reaction following the intravenous injection of 

 potent filtrates. No relation exists between the size and intensity 

 of the primary reaction and the lesion produced upon intravenous 

 injection of reacting factors. 



There are also discussed in this chapter the susceptibility of 

 xarious sites of the rabbit's skin; the possible spreading of the 

 local lesion to adjacent non-prepared skin sites; involvement of 

 regional lymph nodes; the effect of Reynal's spreading factors 

 upon intensity and size of lesions of the phenomenon; and the 

 possible superadded effect of Julianelle and Reimann's pmpuro- 

 genic substances. 



The quantitative estimations of potency of active principles of 

 the phenomenon may be made by the use of three methods: 



Reciprocal titrations of various skin-preparatory doses against 

 \arious reacting doses (Method I) ; titrations of skin-preparatory 



