Patients with idiopathic acquired cold-induced urticaria were evaluated for the release of the preformed mast-cell mediators of immediate-type hypersensitivity during a study in which one arm was immersed in ice water while the other arm remained as a control. Blood specimens were obtained from each arm serially over a one-hour interval, and serum speciments were assessed for histamine, eosinophil chemotactic factor of anaphylaxis, and complement components. Levels of histamine and eosinophil chemotactic factor rose in the arm subjected to cold immersion for three minutes, with peak values occurring between two and five minutes and returning to base line by 30 minutes. No changes occurred in the control arm or in the immersed arm of normal subjects. Assessment of the classical and alternative complement pathways showed no abnormalities. This initial observation of release of eosinophil chemotactic factor of anaphylaxis in vivo along with histamine assigns the mast cell a central role in cold urticaria.