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Abstract: Endogenous opioid peptides like endomorphins, met-enkephalin and NPFF/FMRFamide family of neuropeptides, besides playing a role in modulation of antinociception, also affect cardiovascular system. Based on MERF, which consists of overlapping sequences of FMRFa and met-enkephalin, two chimeric peptides YGGFMKKKFMRFamide (YFa) and [d-Ala2] YAGFMKKKFMRFamide ([d-Ala2] YFa) were designed and synthesized. In this study, effect of YFa and [d-Ala2] YFa on arterial blood pressure and heart rate was evaluated in anaesthetized rats. Both YFa and [d-Ala2] YFa showed a dose-dependent fall in mean arterial pressure in dose-range of 13–78 μmol/kg. After naloxone treatment (5 mg/kg), vasodepressor effect of [d-Ala2] YFa and YFa was only partially blocked as compared to met-enkephalin. Partial blockade of vasodepressive effect of YFa and [d-Ala2] YFa by naloxone may be attributed to interaction of these chimeric peptides with receptors other than naloxone-sensitive receptors such as anti-opioid receptors, adrenergic receptors and D-analogue receptors. [Copyright &y& Elsevier]