Bronchial challenge by eucapnic voluntary hyperventilation is based on the stimulation of inflammatory cells and nerve endings of the airways and for this reason is considered as an indirect challenge test. Hyperventilation is associated with increased loss of water from the bronchial mucosa, causing a rise in the osmolarity of the mast cell microenvironment, which eventually releases numerous mediators, as histamine, prostaglandins and leukotrienes. To a lesser extent this effect is enhanced by the stimulation of the airway nerve endings and by the cooling-rewarming sequence. The test bears a strong association with markers of inflammatory airway disease and allows adjustment of anti-inflammatory treatment and more effective disease follow-up. It is also an extremely specific test for the diagnosis of bronchial asthma and it is considered as the test of choice for the diagnosis of exerciseinduced asthma. During the test the subject is encouraged to hyperventilate, in order to achieve and sustain particular target ventilation, which varies according to protocol employed. Eucapnia is sus tained via the simultaneous administration of CO2, while response is quantified by measuring the drop in FEV1. The test is considered positive when the drop is greater than 10%. Eucapnic hyperventilation challenge is considered an extremely safe test. Pneumon 2006, 19(1):24-35.