Lead poisoning in adults remains a common and serious illness in the United States. Recent studies on children and adults have raised new concerns about adult exposures that were previously felt to be without health risk. Public health practitioners and policy makers must readdress long held assumptions about the safety of lower dose exposure to lead. Clinicians caring for patients with increased lead absorption bare faced with urgent questions about risks and benefits of clinical interventions which cannot be answered with present knowledge. Studies of the consequences of previous exposures and controlled trials of clinical intervention will require the use of more sensitive and specific markers of lead dose and lead effect than have been heretofore available. An important new marker of dose, bone lead measurement by x-ray fluorescence (PbXRF), and two new biomarkers of effect, renal lead binding protein (RLBP) and carboxy-copro and uroporphyrins (CCUP) have recently become available. These new biomarkers appear to be more accurate, specific and sensitive than previously available biomarkers. A multi- disciplinary team of investigators propose three closely linked studies to validate these new biomarkers as predictors of long term health effects after lead intoxication, to establish their use in studies of clinical interventions in individuals with elevated body burdens of lead, and to assess their sensitivity for studies of populations with levels of absorption below the range of currently used biomarkers.