This chapter reviews the information available concerning peptidases present in the circulation and in the gastrointestinal tract and their relative contribution to the neuropeptide-inactivating mechanisms taking place in these biological compartments. Homogenates of gastrointestinal tissues allow the determination of their complete content in neuropeptidases and their putative ability to catabolize neuropeptides. An important limitation of Tissue Homogenates and Purified Membrane preparations concerns the fact that no indication of the subcellular localization of the peptidases can be afforded. Tissue slices can be incubated or superfused with solutions containing physiological concentrations of labeled or unlabeled exogenous peptides. This technique allows the establishment of the contribution of cell-surface peptidases. The isolated organ is one of the bioassays that are the most widely employed by pharmacologists. The main advantage of this technique in studies on peptide metabolism is the conservation of the integrity of the structure of the tissue.