The aim of the present study was to investigate the edema induced by leukotriene D4 (LTD4). Edema is the gross effect of increased blood flow and capillary permeability. Our objective was to elucidate the effect of LTD4 on edema generation without the influence of the concomitantly increased blood flow induced by this potent vasodilator. A new method was outlined measuring the exudation through skin windows of a macromolecular tracer [( 131I]albumin) and a micromolecular tracer [( 99Tc]pertechnetat). Exudation of [131I]albumin is a function of enhanced vascular permeability and interstitial transport and blood flow, whereas that of [99Tc] pertechnetat is mainly a function of blood flow. Thus a ratio of the 2 exudate measurements gives a specific estimate of the changes in vascular permeability and interstitial transport. Histamine was employed to establish the method. A dose-response relation was found for histamine in the dose range of 10(-4) to 10(-7) M. The effect of 10(-5) M LTD4 on vascular permeability and interstitial transport of macromolecules was indistinguishable from that of histamine in the same concentration. This property together with their well-known vasodilatory capabilities indicate that the leukotrienes of the slow-reacting substance of anaphylaxis may play a role in the vascular changes in the allergic-inflammatory reaction.