Leukotriene B 4 (LTB 4 ) is a product of the 5-lipoxygenase pathway of arachidonic acid (AA) metabolism. LTB 4 is a potent chemotactic factor for neutrophils and has been postulated to play an important role in a variety of pathological conditions including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. To investigate the role of LTB 4 in dermatitis, we used S-(4-dimethylaminobenzyl)-N-[(2S)-3-mercapto-2-methylpropionyl]-l-cysteine (SA6541), a potent leukotriene A 4 (LTA 4 ) hydrolase inhibitor. SA6541 inhibited LTB 4 production with an ic 5 0 value of 270 nM in vitro. 5-Hydroperoxyeicosatetraenoic acid (5-HPETE) or AA injection induced LTB 4 production and neutrophil influx in mouse ear. SA6541 inhibited 5-HPETE- and AA-induced LTB 4 production and neutrophil influx in mouse ear when administered orally at a dose of 50 mg/kg. SA6541 also inhibited 5-HPETE-induced prostaglandin E 2 (PGE 2 ) production, probably by an indirect effect through the inhibition of LTB 4 production. These results suggest that LTB 4 may be important in the pathogenesis of dermatitides such as psoriasis.