The ultrastructure of the process of degranulation of mast cells of human duodenal mucosa was examined. In normal controls little degranulation was seen, but in persons with false food allergy (pseudo-allergy) considerable degranulation of mast cells was detected. This is consistent with the hypothesis that some persons have an abnormal fragility of duodenal mast cells in the presence of histamine-releasing substances. Incubation of duodenal biopsy material with various histamine-releasing agents (compound 48/80, Concanavalin A, the calcium ionophore A 23187, and anti-IgE) confirmed the susceptibility of duodenal mast cells for antigen non-specific release of histamine, or that mediated by IgE. In a group of patients with immediate-type, anaphylactic, food allergy, mast cells in the absence of antigen are in a normal state, but degranulation occurs on exposure in vitro or in vivo to specific antigen. The susceptibility to degranulation continues in persons cured of their food allergy. This suggests that a clinical cure is not due to a change of susceptibility of duodenal mast cells to release histamine, but is possibly associated with formation of blocking antibodies, and/or a modification in reactivity of basophils and mast cells of other organs.