Intake and uptake of lead in the general population is mainly via the gastro-intestinal (GI) tract. Those biological and biophysico-chemical factors operating in the Gl tract are the main determinants of Pb bioavailability. They include sites of Pb uptake, the physiology of uptake/transport to blood, the stage of development, interactions of Pb with nutrients, and Gl biochemical transformations of ingested material. Lead uptake occurs as ion or complex, from micelles and perhaps by pinocytosis in the infant. Uptake is mainly via the duodenum but other sites can participate, e.g. ileum (pinocytosis) and colon. Transport to blood is by active, carrier-mediated transport and passive diffusion. Uptake may include movement through intercellular tight junctions. Lead uptake is affected by nutrients in the Gl tract, operating synergistically or antagonistically. Iron and calcium interactions are most important and augment those also occurring in vivo in tissues. Liberation of lead from diverse ingested media, e.g. food, paint, soil and dust, mining waste, is affected by their chemical/physical forms, hydrolytic and oxidative processes in gastric fluid and other Gl sites. Such changes in vivo are poorly simulated by in vitro tests. The downward revision of blood lead (Pb-8) levels considered 'safe', to about 0.5 ~mol C 1 (10 ~g dL-t) or lower, causes even sources of moderately bioavailable Pb to become important.