Adverse effects of lead on human health have been recognized for centuries. Nevertheless, current public health measures require a greater understanding of the pathobiology of chronic low level exposure (1-3). Such considerations are related to the question of what level of lead intake is harmful and why specific clinical manifestations of lead poisoning are encountered under particular circumstances. The recognition of factors, both synergistic and antagonistic, which influence the toxicity of lead is essential for adequate understanding of the effects of environmental lead on human health. The immense body of literature already written about lead contains many clues to and impressions of such factors, both adverse and beneficial, modifying the toxicity of lead. This brief review will discuss a number of such factors. Few of these have as yet been subjected to rigorous experimental confirmation. A consideration of antagonisms and synergisms is based on certain assumptions with regard to the metabolism of lead; that is, the daily intake and excretion of lead as well as the movement of lead between various tissues and effects on cells and subcellular organelles.