The involvement of leukotrienes in the anaphylactic paw edema was investigated in sensitized boosted or unboosted mice. No difference was noted in the intensity of the antigen-induced paw edema between boosted and unboosted animals. Since the non-steroidal anti-inflammatory agents, indomethacin and aspirin, were inactive, cyclooxygenase products are not involved in the anaphylactic reaction in boosted or unboosted mice. In contrast, the mixed lipoxygenase/cyclooxygenase inhibitor, BW 755C (3-amino-1-m-(trifluoroethyl)phenyl-2-pyrazoline), and the LTD, (leukotriene D,) receptor antagonist, LY 171883 (1-(2-hydroxy-3-propyl-4-(4-(1H-tetrazol-5-yl)butoxy)phenyl)ethaneone, reduced the edema in boosted but not unboosted mice, suggesting the involvement of lipoxygenase metabolites in the allergic edema in boosted mice. Dexamethasone was only effective in inhibiting allergic edema in boosted mice when administered 12 h before provocation, but failed to reduce the edema in unboosted mice. Our results suggest that the booster injection during immunization shifts the anaphylactic mouse paw edema from a leukotriene-independent to a leukotriene-dependent reaction.