Intestinal T cells from gluten sensitivity/celiac disease patients respond to a heterogeneous array of peptides. Our study extended this heterogeneity to humoral immune response to various wheat proteins and peptides in patients with gluten sensitivity or Crohn’s disease. IgG and IgA antibodies in sera from those patients and healthy control subjects were measured against an array of wheat antigens and peptides. In gluten-sensitive patients, IgG reacted most against transglutaminase, prodynorphin, wheat extract, and α-, γ-, and ω-gliadin; IgA reacted most against wheat then transglutaminase, glutenin, and other peptides. In the sera of Crohn’s disease patients, IgG reacted most against wheat and wheat germ agglutinin then transglutaminase, prodynorphin, α-, and γ-gliadin; IgA reacted foremost against prodynorphin then transglutaminase and α-gliadin. These results showed a substantial heterogeneity in the magnitude of IgG and IgA response against various wheat antigens and peptides. Measurements of IgG and IgA antibodies against such an array of wheat peptides and antigens can enhance the sensitivity and specificity of serological assays for gluten sensitivity and celiac disease and may also detect silent celiac disease or its overlap with inflammatory bowel disease.