The issue to be considered is that of the significance of lead in the air, but not that alone, since lead in the food and beverages consumed by people generally must also be taken into account. The magnitude of one of these sources must, of necessity, be adjusted to that of the other. After a consideration of certain general toxicological principles such as the limitations of the term “cumulative poison,” as applied to lead in the ambient atmosphere, the role of physiology is emphasized as the decisive element in the issue. Reliance must be based on the capacity of the human organism to deal effectively with lead absorbed at a low rate, by eliminating it from the body at an equivalent rate, thus promoting a steady state. Criteria for the ideal determination of the tolerable concentration of lead in the ambient air, are stated in physiological terms as follows: The tolerable concentration of the (inorganic) compounds of lead, singly or collectively, in the air breathed by human beings of all ages, sexes, and physical and functional types, can be defined ideally, as that resulting in a rate of absorption of lead into their bodies, which when augmented by that derived from all sources in the common environment other than air, can be eliminated regularly from the body, without permitting a significant degree of progressive accumulation therein, and without inducing or contributing to disease or to the impairment of any essential function of the human organism. A summary of available evidence begins by stating the facts as to the intake and output of lead by various groups of persons in the general population. It proceeds to the results of detailed balance experiments on human subjects under controlled conditions, which indicate that there is indeed an approximate equilibrium between the intake of lead and the output of lead over prolonged periods of time, during which the absorption of lead is limited strictly to that which derives from the food and beverages and from the ambient air. On this background, a review, of the principal contributions to the literature, mainly that of the decade just ending, with respect to the behavior of lead and its inorganic compounds, examined such matters as: (1) The body burden of lead in the general population of the United States. The conclusion is reached that the information obtained thus far by the analysis of the tissues of deceased persons is insufficient to prove the case for or against the accumulation of lead in the body with age. It appears that the balance experiments have yielded more reliable information thus far. (2) The disposition of airborne lead compounds in the human respiratory tract. Quantitative evidence concerning the fate of airborne particulate compounds of lead in the human respiratory tract is limited, largely, to measurements of the retention of the particles in the respiratory tract. Recent experiments have extended this information to apply to the manner of the distribution of the particles within the various parts of the respiratory tract, as determined by their size and the respiratory rate. It is not possible, on present information, to visualize the extent of the clearance of lead from the respiratory tract, and until the mechanisms involved in such clearance have been appraised under a variety of conditions, one cannot measure the absorption of lead from the ambient air in the respiratory tract. An experimental basis for bridging this gap in our knowledge has been advanced. (3) Chemical evidence which is indicative of approaching or impending danger from the absorption of lead compounds. The value of determinations of lead in the blood and of coproporphyrin III and of delta-aminolevulinic acid in the urine, in relation to the absorption of lead under a variety of conditions of exposure to lead has been explored on the basis of the experience and the experimental work of many investigators. The conclusions arrived at may be summarized as follows: The difference between the current levels of the concentration of lead in the blood of persons in the general “normal” population, and of those which are found in individuals and groups of persons who are subjected to potentially dangerous exposure to and absorption of lead, is ample for the purposes of differentiation. The hematological responses to lead absorption by individuals and groups, including the more subtle chemical disturbances in the metabolism of hemoglobin, do not put in their appearance when the rate of absorption remains within the limits encountered in the so-called “normal” population. (4) Unusual susceptibility to the absorption of lead at low rates. It has been suggested that there are certain sensitive groups in the general population, especially young children, pregnant women, and persons with impaired renal function, who may be at considerable disadvantage. It seems unlikely that the history of lead poisoning and its sequelae, which tend to justify a degree of concern for the safety of these, and perhaps for other special groups in the general population, applies to the absorption of lead at the present common environmental level.