The future challenge of lead toxicity.

Five decades ago, lead toxicity in childhood was thought in nonlethal cases to be without residual effect. This misconception was corrected in 1943 by Randolph Byers, who began the modern era of lead neurotoxicology by asserting that lead not only killed cells, but interfered with the normal development of central nervous system neurons. The human data from Byers forward is reviewed, with particular attention on methodological issues that have emerged. The papers on human neurotoxicology presented at the NIEHS lead conference held in Research Triangle Park, NC, in 1974 are examined to demonstrate the progress made over the last 15 years. Seven methodological solecisms have clouded judgment over the question of lead toxicity at low dose: worship of the sacrament of p = 0.05; inaccurate causal modeling; drawing conclusions from studies with inadequate power; positing phantom covariates; underestimating the importance of "small" effects; demanding proof of causality; and evaluating studies in isolation. The principles behind these errors are discussed. Lead exposure is associated with hyperactivity, and hyperactivity is a risk factor for antisocial behavior. The relationship between lead exposure and antisocial behavior is estimated. A plan for the effective removal of one major lead source, housing stock, is presented.