Background: Many review articles report the safety and lack of serious side-effects associated with the histamine challenge. Even though methacholine and hypertonic saline are more commonly used to measure airway responsiveness, histamine challenges are used in many countries around the world. Levels of subjects discomfort after a challenge have not been quantified. This study quantified the incidence, severity and duration of subject discomfort after histamine challenge. Methods: Ninety-nine subjects were recruited in an Australian multi-centre population-based study of the genetic epidemiology of asthma. Subjects completed a histamine challenge with final cumulative dose 3.2 mumol. Immediately, and 10 min, after challenge subjects rated their discomfort for cough, headache, throat irritation, hoarse voice and flushed. Research personnel also reported their perception of subject discomfort. Results: Subjects and research personnel reported a small degree of subject discomfort for all symptoms immediately after the histamine challenge. Overall, median symptom scores were less than 1.5 out of 10. Discomfort scores improved 10 min after challenge and cough, throat irritation and flushed improved significantly Conclusions: This study confirms the tolerability of the histamine challenge, (C) 2002 Elsevier Science Ltd. All rights reserved.