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BACKGROUND AND PURPOSE: Meningeal blood flow is controlled by calcitonin gene-related peptide (CGRP) released from trigeminal afferents and nitric oxide (NO) mainly produced in arterial endothelium. The vasodilatory effect of NO may be due to the NO sibling nitroxyl (HNO), generated through the reaction with hydrogen sulfide (H2 S). We investigated the involvement of HNO in CGRP release and meningeal blood flow. EXPERIMENTAL APPROACH: Blood flow in the exposed rat dura mater was recorded by laser Doppler flowmetry. CGRP release from the dura mater in the hemisected rat head was quantified using an ELISA. NO and H2 S were localised histochemically with specific sensors. KEY RESULTS: Topical administration of the NO donor diethylamine-NONOate increased meningeal blood flow by 30%. Preadministration of oxamic acid, an inhibitor of H2 S synthesis, reduced this effect. Administration of Na2 S increased the flow by 20%. This effect was abolished by the CGRP receptor antagonist CGRP8-37 or the TRPA1 antagonist HC030031 and reduced when endogenous NO synthesis was blocked. Na2 S dose-dependently increased CGRP release 2-3-fold. Co-administration of diethylamine-NONOate facilitated CGRP release, while inhibition of endogenous NO or H2 S synthesis lowered basal CGRP release. NO and H2 S were mainly localised in arterial vessels, HNO additionally in nerve fibre bundles. HNO staining was lost after the treatment with L-NMMA and oxamic acid. CONCLUSIONS AND IMPLICATIONS: NO and H2 S cooperatively increase meningeal blood flow by forming HNO, which activates TRPA1 receptor channels of trigeminal fibres inducing CGRP release. The proposed role of the HNO-TRPA1-CGRP signalling for the pathophysiology of headaches is discussed.