Rabbit antibodies specific for human γE released histamine from the leukocytes of atopic patients, whereas antibodies specific for the other immunoglobulin classes did not. Antibodies specific for the light chains of immunoglobulins also released histamine. The results indicated that the histamine release is a reversed type allergic reaction. The concentration of anti-γE required for 50% histamine release from leukocytes varied, depending on the donors. This concentration roughly correlated with the minimal concentration of the same antibody required to induce erythema-wheal reactions in their skin but was unrelated to the γE concentration in their sera. The sensitivity of leukocytes to anti-γE was increased by passive sensitization of the cells with reaginic serum containing a high concentration of γE. The results showed that γE is present on/in leukocytes and that γE antibodies on the cells are responsible for histamine release by allergen.