Blood from forty-one persons with atopic disease was incubated with various concentrations of specific antigen. The amount of histamine released into the plasma was measured chemically. Histamine was released by concentrations of pollen extract as low as 0.01 meg. protein nitrogen per liter of blood; more histamine was released by greater amounts of antigen until a maximum level was reached at antigen concentrations of from 4 to 20 meg. P.N. per liter of blood. Histamine release tended to be suppressed by high concentrations of antigen unless massive amounts were used (4,000 meg. P.N. per liter of blood), at which point nonspecific release occurred. The degree of skin reactivity of the subjects studied was related inversely to the antigen concentration producing maximal histamine release. The rate of histamine release was apparently linear, maximum release being approached only after at least thirty minutes of incubation of blood with the specific antigen.