Nonspecific hyperresponsiveness to adenosine monophosphate is better related to airway inflammation than methacholine. Adenosine induces mast cells and other cells to release inflammatory mediators that produce bronchoconstriction and perhaps other inflammatory effects, such as plasma exudation, which have not been well studied. We compared the plasma exudation effect, as measured in induced sputum, between adenosine and methacholine challenge in healthy and asthmatic subjects. In a cross-over design, 42 subjects were randomly challenged with adenosine or methacholine. After recovery, induced sputum was collected on 2 separate days, 48 to 72 hours apart. In the control group, an additional challenge with saline was performed. Differential cell counts and albumin and alpha2-macroglobulin levels were determined. The sputum volume obtained was sufficient to measure proteins in only 34 subjects: 10 healthy individuals and 24 mild asthmatics. There was a significant difference between adenosine and methacholine in sputum albumin (mean differences: 68[73.4] microg/L in controls, p = 0.039 and 48.0[162.9] microg/L in asthmatics) and cell counts, but only a tendency in alpha2-macroglobulin. PC20 adenosine was better related to eosinophil counts than methacholine (r = -0.44, p = 0.014). Albumin or alpha2-macroglubulin levels were not significantly correlated with baseline FEV1, PC20, or eosinophil counts. Adenosine, but not methacholine challenge, produces a mild airway plasma exudation that does not seem to be relevant to bronchoconstriction. However, this could be relevant, to some supernatant measurements after adenosine challenge.