We undertook this study to determine whether patients with late-onset hypogammaglobulinemia, who are at very high risk for gastric cancer, have a reduced secretion of gastrin after stimulation with food or bombesin, a potent gastrin-releasing stimulus. We compared the plasma gastrin responses to bombesin and to a standard test meal in 18 patients with late-onset hypogammaglobulinemia with those in patients with X-linked agammaglobulinemia, early-onset hypogammaglobulinemia, or hypogammaglobulinemia due to lymphoproliferative cancer, and in 30 normal control subjects. Thirteen of 18 patients with late-onset hypogammaglobulinemia (72 percent) had an abnormally low gastrin response to bombesin, as compared with none of 21 patients with other forms of hypogammaglobulinemia (P less than 0.05). After a test meal, abnormally low gastrin secretion was found in 6 of 14 patients with late-onset hypogammaglobulinemia (43 percent) and in 1 of 18 patients with other forms of the disease (6 percent) (P not significant). The plasma gastrin responses to stimulation with bombesin or food distinguished late-onset hypogammaglobulinemia from other forms, with sensitivities of 72 and 43 percent and specificities of 100 and 94 percent, respectively. Stimulated gastrin response can therefore be used as a marker for this type of immunodeficiency. The test responses also showed heterogeneity among patients with late-onset hypogammaglobulinemia and may help to identify patients with an increased risk for gastric cancer.