1. The cutaneous responses of rabbits to small doses of horse serum intracutaneously is described. After an original injection of 0.1 cc. a secondary reaction often occurs about the 9th day, and tests at 3 day intervals with 0.001 cc. quantities indicate that general skin hypersensitivity is established at this time. Circulating precipitins for horse serum appear later. As the degree of sensitivity increases, lesions resulting from test doses reach a maximum development more quickly.
2. The reactivity of rabbits to horse serum is greatly increased by antecedent sensitization of the animals with repeated small intracutaneous inoculation of indifferent streptococci or immunization with large intravenous injections of either indifferent or hemolytic streptococci. Doses of indifferent streptococci precisely comparable to those producing greatly enhanced reactivity when given intracutaneously, increase reactivity to horse serum irregularly and to slight degree when injected intravenously.
3. Increases in reactivity (allergic irritability) are made evident by the occurrence of larger skin lesions at the site of the primary horse serum injections, the earlier development of more distinct secondary reactions in a higher percentage of animals, and by the more rapid appearance of skin sensitivity to the small test doses which may be first evidenced by delayed reactions at these injection sites. Accompanying these evidences of increased reactivity, there is an early appearance of blood serum precipitins in high titer.
4. There was no evidence of residual inflammation in any of the animals at the time reactivity to horse serum was tested. No attempt was made to determine the duration of this altered reactive capacity. It has been encountered in tests begun from 8 to 14 days after the last preliminary inoculation.
5. It is suggested that the increased reaction described is brought about by a persisting alteration in the functional activity of the reticulo-endothelial system.