To establish whether a relationship exists between cutaneous and bronchial reactivity to leukotriene D4 (LTD4), endpoint cutaneous reactivity and bronchial reactivity were determined in six patients with asthma, six patients with seasonal allergic rhinitis, and six nonatopic men. In all subjects, increasing doses of LTD4 produced decreases in specific airway conductance (SGaw) and flow at 30% of vital capacity measured from a partial forced expiratory maneuver (V30P). Intracutaneous injections of LTD4 and histamine resulted in immediate wheal and erythema reactions in all patients. Serial 10-fold dilutions of LTD4 and histamine were injected to establish the lowest dose capable of producing a 4 mm wheal with erythema. Endpoint cutaneous reactivity to LTD4 ranged from 1 mumol to 100 pmol in controls and from 100 nmol to 1 fmol in patients with asthma, but statistically significant differences between groups were not apparent even with inclusion of six additional subjects. No meaningful correlations were found between the quantity of LTD4 producing the threshold cutaneous reaction and the dose of inhaled LTD4 that produced a 35% decrease in SGaw and 30% decrease in V30P. In contrast to the bronchi, where subjects in all three groups were 264 to 840 times more sensitive to LTD4 than to methacholine, 11/18 subjects (3/6 with asthma) were less sensitive to LTD4 than to histamine in terms of endpoint cutaneous reactivity. However, seven of 18 subjects who were more sensitive to LTD4 than to histamine had relative potencies ranging from 5 to 500,000.