The principal catabolic pathways are believed to be known and most of the major excretory products have been identified. Future progress in the enzymology of histamine (H) breakdown, a field in which many interesting problems await investigation, requires formulation of a satisfactory system of nomenclature. For characterization of these enzymes, some of which appear to be quite delicate in vitro, use of minute quantities of substrate seems to be advantageous and may be essential in some cases. Evidence is required on the importance of side chain N-methylation of H in mammals. Nonoxidative reactions of imidazoleacetaldehyde and methylimidazoleacetaldehyde should be studied. On the basis of available knowledge of H catabolism several approaches are suggested for the evaluation of the role of H formation or release in physiological and pathological states in living animals. The first is useful only in the female rat; aminoguanidine is given and H determined. The 2d is use of aminoguanidine plus a methylation inhibitor (not yet known) and determination of H. The 3d is use of aminoguanidine plus iproniazid and determination of I,4-methylhistamine. The 4th, preferable because it does not require inhibitors, is determination of 1,4-methylimidazoleacetic acid. A satisfactory method for the determination of this compound might help resolve the conflicting reports on the physiological and pathological roles of H.