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The thromboxane A<jats:sub>2<\/jats:sub>(TXA<jats:sub>2<\/jats:sub>) mimetic U-46619 significantly increased N-arachidonylethanolamine (AEA) and 2-arachidonylglycerol (2-AG) content of isolated MCA, whereas 5-hydroxytrypamine (5-HT) decreased AEA and 2-AG content. If eCBs play a feedback role in the regulation of MCA tone, then CB<jats:sub>1<\/jats:sub>receptor antagonists should enhance the constriction of MCA produced by U-46619 but not 5-HT. U-46619 caused concentration-dependent constrictions of endothelium-denuded MCA. Two CB<jats:sub>1<\/jats:sub>receptor antagonists SR-141716 and AM-251 decreased the EC<jats:sub>50<\/jats:sub>value for U-46619 to constrict endothelium-denuded MCA without affecting the maximal effect. A low concentration of CB<jats:sub>1<\/jats:sub>receptor agonist Win-55212-2 (30 nM) produced vasodilation of MCAs constricted with low but not saturating concentrations of U-46619. SR-141716 had no effect on the 5-HT concentration-contraction relationship. These data suggest that TXA<jats:sub>2<\/jats:sub>receptor activation increases MCA eCB content, which, via activation of CB<jats:sub>1<\/jats:sub>receptors, reduces the constriction produced by moderate concentrations of the TXA<jats:sub>2<\/jats:sub>agonist. Although 5-HT-induced vasoconstriction is reduced by exogenous CB<jats:sub>1<\/jats:sub>receptor agonist, activation of 5-HT receptors does not increase eCB content. 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