Bronchial hyperresponsiveness (BHR), the increased sensitivity to a wide variety of stimuli that narrow the airways, is a central abnormality in patients with asthma, and is frequently observed in patients with chronic obstructive pulmonary disease. In the study of the underlying mechanisms of BHR, various animal models have been employed, using methods of active and passive immunization. These studies have led to a changed understanding of smooth muscle hyperreactivity, questioning both the past paradigm of altered neural activity and the modern concepts of inflammation as the single most factor determining BHR, and emphasizing the particular importance of the end organ- the smooth muscle cell. More recently, passive sensitization of human airways has been used by several investigators to describe the mechanisms of allergic sensitization and to study the role of functional abnormalities of human airway smooth muscle, which may represent the key to understanding human BHR, and thus lead to novel treatment approaches for the future.