Bradykinin (BK), a pro-inflammatory factor and vasodilator, causes functional change of the small artery. However, it is not clear whether any of these changes induced by BK are mediated or not by ceramide. Therefore, we investigated whether BK affects the hydrolysis of shingo-myelin and generation of ceramide in the intact rat small artery. Our results suggest that BK induces sphingomyelin hydrolysis and increases ceramide production in a time- and dose-depen-dent manner. Relative to controls, BK causes a 50% decrease in sphingomyelin levels. Ceramide levels increase in response to BK with the highest level being obtained with 10-8 M BK within 30 min. Similar amounts of ceramide are generated when exogenous SMase is added to the rat small arteries. We next determined which of the two BK receptors (BK-B1 antagonist; Lys-Des-Arg9-Leu8-BK or BK-B2 antagonist Hoe-140) are implicated in the BK-induced generation of cera-mide. The BK-B2 antagonist did not alter the effect of BK on ceramide generation whereas the BK-B1 antagonist blocked the BK-induced production of ceramide. While having no effect on KCl-induced constrictions (45 mM K+), ceramide dilated pre-constricted (Phenylephrine) small pressurized (60 mm Hg) rat mesenteric arteries by ~ 40 %. These results suggest that the activa-tion of the BK-B1 receptor mediates the BK-induced activation of SMase and of the concomitant production of ceramide. And finally, BK-mediated effects on vascular tone may be due, at least in part, to the increased production of ceramide.