BACKGROUND: While clinical trials with antileukotrienes have shown overall beneficial effects in asthma, the factors that determine leukotriene dependent asthma are still unclear. A study was undertaken to determine whether or not leukotriene responsiveness in the airways correlates with endogenous leukotriene biosynthesis. METHODS: Bronchial responsiveness to leukotriene (LT) D4 was assessed as PD20FEV1 in 20 subjects with mild asthma and 10 healthy controls, and compared with bronchial responsiveness to methacholine and two global measures of leukotriene production-urinary LTE4 and ex vivo production of LTB4 in whole blood. RESULTS: In patients with asthma the bronchoconstrictor activity of LTD4 was about 1300 times greater than methacholine (geometric mean PD20 0.69 nmol v 887 nmol). Those who were most responsive to LTD4 were relatively less responsive to methacholine (p<0.01). There was, however, no correlation between bronchial responsiveness to LTD4 and urinary LTE4 or blood ex vivo LTB4 levels in asthmatic subjects or healthy controls. Subjects with asthma treated with inhaled corticosteroids produced higher levels of LTB4 (p<0.05). CONCLUSIONS: General measures of leukotriene production cannot predict bronchial responsiveness to LTD4. The unique bronchoconstrictive potency of LTD4 on human airways may relate to the locally regulated expression of the cysteinyl LT1 receptor.