Preparation of radioactive iodine labeled iodoamphetamine (IMP) or I-123 hydroxyiodobenzyl propanediamine (HIPDM) is usually achieved by an iodine-iodine isotope exchange reaction. The initial uptake of IMP and HIPDM in the brain is due to their high lipid solubility. Based on the pH-shift hypothesis, an iodinated diamine, HIPDM, was developed as a brain perfusion imaging agent. Both IMP and HIPDM have been studied extensively in animals as a quantitative regional cerebral perfusion agent. Most of the clinical evaluations have been conducted using either IMP or HIPDM. The chapter provides the discussion on the chemistry, pharmacology and clinical applications of these two agents. Since both IMP and HIPDM are amines with structures that can conceivably interact with neuronal or cellular receptors, it has been proposed that receptor binding may be the mechanism responsible for brain retention. The lung uptake and retention of IMP and HIPDM appear to be related to a specific and saturable "binding" process.