The rectal gland has nerves that contain the same neurotransmitters as the gastrointestinal tract of which it is an appendage. Some of those neurotransmitters stimulate the secretion by the gland, while others inhibit it. The inhibitory neurotransmitters are discussed in this chapter. Somatostatin inhibits the secretion of chloride by the gland stimulated by VIP, adenosine, forskolin, cyclic AMP and theophylline, and CNP. Thus, somatostatin inhibits the secretion of chloride either at a site distal to all these agents or at each of their sites of action. Bombesin exerts its inhibitory effect indirectly through the release of somatostatin from nerves within the gland. NPY inhibits the secretion of chloride at a site beyond VIP and the generation of cyclic AMP independently of the release of other neurotransmitters. PYY also inhibits the secretion of chloride at a site beyond the generation of cyclic AMP. Cholecystokinin inhibits the secretion of chloride by the gland by a mechanism that depends on neurotransmitter release. The control of secretion of chloride by the rectal gland is clearly quite complicated. It involves the activation of the gland by peptide hormones and inhibition of secretion by feedback loops that include adenosine, ATP, somatostatin, bombesin, NPY, PYY, and cholecystokinin.