Two patients are described who initially developed Crohn's disease followed by hypogammaglobulinemia. The immunologic profile of both was typical of acquired common variable hypogammaglobulinemia. The peripheral blood lymphocytes of neither patient were able to synthesize immunoglobulin when cultured with pokeweed mitogen in vitro nor were cultures containing mixtures of purified B cells and T cells. A potent suppressor T cell was present in the peripheral blood of both patients that was able to completely suppress immunoglobulin synthesis in cultures of normal B cells and T cells. When the patients' B cells were highly purified and appropriately stimulated in vitro, they were able to synthesize immunoglobulin, providing strong evidence that the circulating suppressor T cell was mediating the hypogammaglobulinemia. We have previously shown that many patients with Crohn's disease have a circulating “covert” suppressor T cell that is not expressed in cultures of unfractionated peripheral blood lymphocytes, but which becomes apparent after isolation of their T cells on antiimmunoglobulin columns. We conclude that these 2 patients represent instances in which the ”covert” suppressor T cell of Crohn's disease has become overtly active in the systemic circulation and has resulted in hypogammaglobulinemia. © 1984, American Gastroenterological Association. All rights reserved.