In the bronchi of asthmatic subjects many bronchoconstrictor mediators and neurotransmitters might be released together, and therefore, potential interactions might occur that could be important in airway hyperreactivity. We have studied the effect of inhaled methacholine, bradykinin, and prostaglandin D2 (PGD2) on bronchial reactivity to inhaled histamine in 6 mild asthmatic subjects, 22 to 36 yr of age. All of the test spasmogens were given at equivalent bronchoconstricting concentrations. Simultaneous dosing with PGD2 caused a significant increase in reactivity to histamine, mean dose of histamine causing a 35% fall in specific airway conductance being 0.72 mumol before, and 0.32 mumol with, PGD2; (p less than 0.01). This was not seen with histamine itself, methacholine, or bradykinin. Prostaglandin D2 caused a similar increase in bronchial reactivity to inhaled methacholine, suggesting a postreceptor potentiation of airway smooth muscle contractility. This positive interaction between inflammatory mediators known to be released in asthma has important implications for understanding bronchial hyperreactivity.