Hydrogen sulfide (H(2)S) plays an important role in cardiovascular, central nervous, and gastrointestinal systems. Being the third gaseous mediator, H(2)S has been shown to act as a vasodilator. In recent times, more and more attention has been paid to the biological functions of H(2)S in inflammation. Substance P is an 11 amino acid neuropeptide that is released from nerve endings in many tissues. Subsequent to its release, substance P binds to neurokinin-1 (NK-1) receptors on the surface of effector cells and, in addition to being a mediator of pain, it plays an important role in many inflammatory states including asthma, immune-complex-mediated lung injury, experimental arthritis, and inflammatory bowel disease. Substance P has been shown to increase microvascular permeability and promote plasma extravasation. Using animal models of inflammation of different etiologies such as acute pancreatitis, sepsis, and burns, studies in our laboratory have recently shown an important role of the pro-inflammatory action of H(2)S and substance P.