Leukotriene B₄ (LTB₄) is a potent leukocyte chemoattractant, recently implicated in the pathogenesis of atherosclerosis. The aim of this study was to assess the effects of LTB₄ on isolated aortic preparations. Rings of guinea pig aorta were challenged with LTB₄ for recording of mechanical responses and measurements of mediator release, and LTB₄ receptor (BLT₁) receptor expression was assessed by RT-PCR. Single concentrations of LTB₄ induced concentration-dependent contractions that were inhibited by treatment with antihistamines, indomethacin or the TP receptor antagonist BAYu3405, as well as by denudation of endothelium. In addition, LTB₄ increased the release of histamine and thromboxane in the bath. The contractions induced by LTB₄ were inhibited by either the unselective BLT receptor antagonist ONO-4057 or the selective BLT₁ receptor antagonist U-75509. Pre-treatment with alltrans retinoic acid enhanced the contractions and the release of histamine induced by LTB₄, without affecting either the contractions induced by histamine, or the histamine release evoked by calcium ionophore A23187. Analysis by RT-PCR indicated the expression of a BLT₁ receptor in the guinea pig aorta, and that BLT₁ receptor mRNA was up-regulated after treatment with retinoic acid. These results suggest that LTB₄ contracts the guinea pig aorta via an indirect mechanism involving the release of histamine and thromboxane and that this BLT₁ receptor mediated response can be upregulated by all-trans retinoic acid.