Arachidonic acid metabolites such as prostaglandins and leukotrienes have been shown to play an important role in the pathogenesis of otitis media (OM). Among these mediators, leukotriene B4 (LTB4) is one of the most potent inducers of inflammatory processes. SC-41930 has been shown to be a specific LTB4 receptor antagonist both in vitro and in vivo. In this study, anti-inflammatory effects of SC-41930 were investigated in a guinea pig model of OM induced by middle ear (ME) inoculation of killed Staphylococcus aureus. Outcome of treatment was determined by measurement of myeloperoxidase activity in the samples of ME mucosa, evaluation of temporal bone histopathology, and presence of ME fluids. Myeloperoxidase activity in the SC-41930-treated group was found to be significantly lower than that in the control group. Histopathology of temporal bones indicated decreased inflammation in the treated group as compared to the controls. In addition, ME fluids were absent in four out of six treated animals. These results demonstrate that SC-41930 can produce significant anti-inflammatory effects in this model of OM.