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Hydrogen sulfide (H2S) is a gaseous transmitter involved in the control of vascular homeostasis. H2S is formed endogenously from l-cysteine or l-methionine by two enzymes, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), and normally circulates in blood. Studies from the past few years have demonstrated the involvement of H2 Sin erectile mechanisms in animal and human tissues. Exogenous H2S relaxes human and animal tissues in vitro and increases intracavernous pressure in experimental animal models. Electrical field stimulation studies on animal and human tissues have demonstrated that endogenous H2S is involved in the physiological control of penile tone. In humans, both CBS and CSE are widely expressed on trabecular muscle, implying that the smooth muscle component is the major source of H2S. Thus, the l-cysteine-H2S pathway may represent a promising target for development of new therapeutics for erectile dysfunction.