During translocation processes, particles may escape macrophage phagocytosis and enter the interstitium. Controlled exposure to defined particles, have allowed direct measurement of translocation processes in extra pulmonary organs. Uptake into the interstitium has an inverse particle-size dependency but is also species dependent. Rats tend to accumulate more particles in the lumen of alveolar ducts and alveoli; humans retain more material in the interstitium. Once in the interstitium, tiny fractions may translocate to extra pulmonary organs. The plausible pathway suggested is transport from lung epithelium into the pulmonary vasculature and lymphatics then into systemic circulation and so reaching other organs. The liver appears to be the preferred target organ of most of the translocated particles. Translocation to the lymph node is rather a process of clearance related to inflammation than of particle size per se. One prerequisite for extra pulmonary site and rate translocation is the form of particle administration technique and poor solubility, indicative that chemical composition and physical structure of the test material may be an important determinant influencing systemic translocation of particles. It has been suggested that the origin of the particles may play an important role in translocation. Test particles (nano and/or microsized) generated under laboratory conditions show a different translocation behaviour compared to industrially-generated (nano)particles. Nanoparticles appear to form agglomerates which, once deposited in the lung, do not appear to disintegrate into smaller nano-sized particles or translocate outside the lung draining lymph nodes.