We measured lung function and airway reactivity to histamine administered by aerosol in two groups of ponies. Principal ponies had a history of heaves, a disease characterized by recurrent airway obstruction when ponies are housed in a barn and fed hay; control ponies had no history of airway obstruction. Ponies were paired (principal and control) and measurements were made when principal ponies were at pasture and in clinical remission (period A), following barn housing when principal ponies had acute airway obstruction (period B), and after a further 1 and 2 wk at pasture (periods C and D). At periods A, C, and D dynamic compliance (Cdyn), pulmonary resistance (RL), arterial O2 tension (PaO2), and CO2 tension (PaCO2) of principals and controls did not differ. Barn housing (period B) decreased Cdyn and PaO2 and increased RL in principals but not controls. The ED65Cdyn (the dose of histamine to reduce Cdyn to 65% of base line) did not differ in principals and controls at periods A, C, and D. At period B, ED65Cdyn decreased by 2.5-log doses of histamine in principals while ED65Cdyn was not affected in controls. There was no correlation between changes in airway reactivity and changes in RL and Cdyn. We conclude that ponies in clinical remission from heaves are not hyperreactive to histamine aerosol. This model of lung disease is similar to some forms of industrial asthma in which hyperreactivity occurs only during acute airway obstruction. The lack of correlation between ED65Cdyn and the degree of airway obstruction suggests that the hyperreactivity of principal ponies to histamine aerosol cannot be explained solely by alterations in baseline airway caliber.