Summary The paradoxical acute exacerbation of pre-existing chronic idiopathic urticaria accompanied by intense generalized pruritus, facial oedema, and dyspnoea in a 36-year-old-woman 3–4 h after a single oral dose of 10 mg cetirizine (Zyrtec® tablets), suggested the presence of an underlying intolerance reaction. However, a type I hypersensitivity reaction also had to be excluded. Detailed allergy testing supported the view that the patient had suffered an intolerance reaction to cetirizine. This is the third known case of most probably a nonallergic generalized urticaria following the administration of cetirizine, a drug with extensive usage worldwide. However a type I sensitization to cetirizine is indeed possible, as has been demonstrated in this research with the verification of cetirizine-specific IgE antibodies in one of the control sera.