Context: Different kinds of gums from various sources enjoy an extremely broad range of commercial and industrial use, from food and pharmaceuticals to printing and adhesives. Although generally recognized as safe by the US Food and Drug Administration (FDA), gums have a history of association with sensitive or allergic reactions. In addition, studies have shown that gums have a structural, molecular similarity to a number of common foods. A possibility exists for cross-reactivity. Objective: Due to the widespread use of gums in almost every aspect of modern life, the overall goal of the current investigation was to determine the degree of immune reactivity to various gum antigens in the sera of individuals representing the general population. Design: The study was a randomized, controlled trial. Participants: 288 sera purchased from a commercial source. Outcome measures: The sera was screened for immunoglobulin G (IgG) and immunoglobulin E (IgE) antibodies against extracts of mastic gum, carrageenan, xantham gum, guar gum, gum tragacanth, locust bean gum, and β-glucan, using indirect enzyme-linked immunosorbent assay (ELISA) testing. For each gum antigen, inhibition testing was performed on the 4 sera that showed the highest IgG and IgE immune reactivity against the different gums used in the study. Inhibition testing on these same sera for sesame albumin, lentil, corn, rice, pineapple, peanut, pea protein, shrimp, or kidney bean was used to determine the cross-reactivity of these foods with the gum. Results: Of the 288 samples, 4.2%-27% of the specimens showed a significant elevation in IgG antibodies against various gums. Only 4 of 288, or 1.4%, showed a simultaneous elevation of the IgG antibody against all 7 gum extracts. For the IgE antibody, 15.6%-29.1% of the specimens showed an elevation against the various gums. A significant percentage of the specimens, 12.8%, simultaneously produced IgE antibodies against all 7 tested extracts. Conclusions: Overall, the percentage of elevation in IgE antibodies against different gum extracts, with the exception of carrageenan, was much higher than for the IgG antibody. The results of the current study showed that a subgroup of healthy individuals who produced not only IgG but also IgE antibodies against various gums may suffer from hidden food immune reactivities and sensitivities. Further study is needed to examine the clinical importance of gums and cross-reactive food antibodies in symptomatic individuals.