Plasma histamine in 8 normal subjects was measured before and after inhalation of carbachol to induce a 50% fall in specific airway conductance (SGaw). The measurements were repeated 5 min after inhalation of salbutamol or placebo. No significant change in plasma histamine occurred after placebo or carbachol inhalation, despite the persistent induced bronchospasm after the latter treatment. In contrast, plasma histamine was significantly increased from 0.25 to 0.43 ng/ml after salbutamol inhalation. Simultaneously, induced bronchospasm was relieved, from 51% to 103% of baseline SGaw. Thus, the relief of carbachol-induced bronchospasm by salbutamol was associated with a rise in plasma histamine. Since salbutamol itself is a potent inhibitor of mast cell degranulation and histamine release, the present findings suggest that histamine may be released and sequestered within the lungs during carbachol-induced-bronchospasm, and also that desequestration of bronchoconstrictor mediators accumulated at the point of contact of bronchial smooth muscle may contribute to the relief of bronchospasm by salbutamol.