The process of nebulization and deposition of LTD₄ was studied in detail. The concentration of LTD₄ in a saline solution decreased by approximately 90 % after 2 min of nebulization in a DeVilbiss 35B ultrasonic nebulizer. This decrease was prevented by diluting LTD₄ in a phosphate buffer, pH 7.4. Nebulization of tritiated LTD₄ in this phosphate buffer did not cause any appreciable deterioration of the leukotriene, as demonstrated by an unchanged ratio between radioactivity and LTD₄ concentration in the test solution before and after nebulization as well as in the condensed aerosol. The aerosol generated by the DeVilbiss 35B ultrasonic nebulizer was shown to generate particles with a mass median diameter of 1.3 microns (dry particle size). Interposition of a settling bag reduced the amount of large particles, reducing the mass median diameter to 0.84 microns (dry particle size). Nine healthy volunteers were challenged on separate days with 40 nmol LTD₄ or 100 nmol histamine, and the changes in FEV, and partial flow volume curves initiated at 50% of vital capacity (V_max30) were measured. A relative diffuse deposition pattern was ensured by inhalation via a settling bag. These results were compared to challenges with a relatively central deposition pattern as ensured by inhalation directly from the nebulizer with brisk inhalation maneuvers. The diffuse deposition pattern caused minimal changes in FEV, but pronounced effect in V_max30. The effects of LTD₄ and histamine on FEV, and V_max30 changed in parallel when the deposition of the mediators was changed to a more central pattern. This indicates that the two mediators do not differ with respect to any selective effects on different parts of the airways.