Wheat, milk, peanuts, soy, egg and corn are among the most major sources of immunoreactive proteins. The first goal of this study was to examine the reactivity of food specific antibodies with human tissue antigens. Affinity‐purified rabbit anti‐food antibodies were applied to 65 tissue antigens. Anti‐peanut antibody had the most reactions with 24 out of the 65 antigens, followed by anti‐alpha‐gliadin with 20, anti‐egg with 17, anti‐wheat with 15, anti‐milk with 14, and both anti‐corn and anti‐soy with 10 each tissue antigens. Serial dilutions and inhibition study confirmed that these reactions were specific. The second goal was to determine the percentage of blood donors with elevations in IgG, IgA, IgM and IgE antibodies against these food antigens. A significant percentage of the tested blood samples showed elevations in antibodies against different food antigens. This reaction of food‐specific antibodies with different tissue antigens indicates that cross‐reactivity between food and human tissue antigens exists, and these antibodies, if detected in blood, may contribute to different autoimmune diseases.