An inhibitor of histamine release was found to be associated with the human eosinophilic leukocyte. This eosinophil-derived inhibitor (EDI) was released from eosinophil-rich fractions upon sonication or interaction with immune reactants (specific allergens or anti-IgE). EDI was found to exert its inhibitory action at the target cell level by increasing the intracellular levels of cyclic-AMP. Preliminary electron microscopic studies show the presence of IgE on the eosinophilic leukocyte and it is suggested that the allergen or anti-IgE-induced release of EDI might be due to a direct interaction of these immune reactants with the eosinophil-bound IgE antibody. The results also suggest that by virtue of liberating a histamine release inhibitor such as EDI, the eopsinophil assumes a modulating role in the allergic inflammatory reaction.