The detailed investigation of regional differences in lung function at a local level began when suitable gamma-ray emitting isotopes and focused external radiation detectors (especially the Anger gamma-camera) became available. A major recent advance has been the development of positron emission tomography (PET), which provides a powerful combination of highly accurate tomographic reconstruction of radioisotope concentration with a potentially unlimited list of biological compounds to be labelled with the positron emitting isotopes of oxygen, carbon and fluorine. Early studies using PET focused on the inhalation of 11CO (or C15O) and 19Ne gases and the intravenous injection of 13N in saline and H215O for the measurement of relatively simple aspects of regional lung function, such as tissue, blood and gas volumes, blood flow, ventilation and ventilation/perfusion (V'A/Q'). More recent work has been directed towards the more challenging areas of regional endothelial permeability, carbohydrate utilization, enzyme and receptor binding assays, and in vivo pharmacokinetics. The short physical half-lives of the isotopes (17 s to 2 h) and the noninvasive nature of PET allows serial measurements to be made on patients (within the constraints of permitted radiation doses) to assess the effect of physiological and therapeutic interventions.