Only two of 41 legume-allergic patients diagnosed by double-blind, placebo-controlled oral food challenge or “convincing history” of anaphylaxis had an IgE-mediated hypersensitivity reaction to more than one member of the legume family. However, extensive immunologic cross-reactivity was demonstrated among legume antigens on Immunoblot and Immunodot-blot analyses and prick skin tests. The proteins of six legumes (peanut, soybean, lima bean, pea, garbanzo bean, and green beans) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, and probed with sera from six legume-allergic patients. Multiple IgE-binding bands were identified in each legume lane by the sera from each of these legume-allergic patients. In vitro cross-reactivity did not correlate with clinical hypersensitivity. All the legumes studied (except green bean) had a prominent band at 20 kd. Numerous proteins and protein subunits can be identified in each of the legumes (16 peanut, 21 soybean, 23 lima bean, 25 pea, 22 garbanzo bean, and 11 green bean protein bands) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and it appears that legume-allergic patients' sera may recognize multiple similar fractions from each legume. A second in vitro test was performed in which the six legume extracts were bound directly onto nitrocellulose paper. These “legume” Immunodot blots were probed for specific IgE-binding activity with sera from 62 patients with positive legume prick skin tests. The legume Immunodot blots again demonstrated extensive clinically irrelevant cross-reactivity. However, this test may prove useful as a simple technique for screening food-specific IgE with minimal quantitites of sera.