A model of immediate-type hypersensitivity (ITH) in the dog using keyhole limpet haemocyanin (KLH) as the antigen was studied. Long-lasting ITH was induced in fifteen of sixteen dogs by the i.v. (Kepron & Tse, 1975), intradermal (Rockey, Schwartzmann & Halliwell, 1971), inhalation (Patterson & Kelley, 1974) and i.d. plus inhalation (Rockey et al., 1971) routes. This ITH was demonstrated by direct skin reactivity, acute respiratory reactions and peripheral blood leucocyte and respiratory cell histamine release. The reaginic antibodies considered to mediate these reactions were larger than canine IgG, heat labile, 2-mercaptoethanol sensitive, and are probably canine IgE. In addition to cutaneous and respiratory reactions, these reagins were shown to mediate systemic reactions. In the course of these studies, an unexpected finding was the occurrence of ITH to KLH in three dogs which had had no prior experimental exposure to KLH. This ITH was of sufficient intensity to be associated with acute airway reactions to the inhaled antigen.