Inhaled acetaldehyde and adenosine 5'-monophosphate (AMP) cause bronchoconstriction in asthmatics by a mechanism believed to involve histamine release from airway mast cells. This study investigates the repeatability of the acetaldehyde challenge and the relationship between airway responsiveness to acetaldehyde and AMP. To this end, we examined the effect of inhaled acetaldehyde on airway tone in comparison with either methacholine or AMP in 16 asthmatics. Furthermore, the repeatability of the acetaldehyde challenge was assessed in 14 subjects with mild asthma. The response to each bronchoconstrictor agent was measured by the PC20 (provocative concentration required to produce a 20% fall in FEV1). The geometric mean (range) PC20 values were 3.1 mmol/l (0.5-46.0 mmol/l) for methacholine, 883.1 mmol/l (190.7-1816.1 mmol/l) for acetaldehyde, and 50.1 mmol/l (3.2-1152.1 mmol/l) for AMP. Thus, acetaldehyde was 18-fold less potent than AMP in causing bronchoconstriction. A similar correlation was observed between PC20 acetaldehyde and either PC20 AMP (r = 0.58, p = 0.02) or PC20 methacholine (r = 0.56, p = 0.02). The challenge procedure with acetaldehyde was moderately repeatable (coefficient of repeatability = +/- 1.4 doubling concentrations, intraclass correlation coefficient = 0.64). We conclude that inhaled acetaldehyde is less potent than AMP in causing bronchoconstriction in asthma, and that the response to inhaled acetaldehyde is repeatable. Furthermore, the present data lends indirect support to the suggestion that acetaldehyde responsiveness and AMP responsiveness are not identifying the same alterations in the airways.