Lead absorption and prevention of the serious effects of lead poisoning are re-examined from the viewpoints of the critical organ and critical effect concepts and the associated dose-effect and doseresponse relationships. If the critical organ is the first affected and the critical effect is the first measurable adverse effect, intervention on this basis should prevent the occurrence of later, more serious effects. In the range of lead absorption of greatest current pediatric concern (blood lead in the range of 50 to 80 μg/dl), blood lead values are not a good predictor of critical effect, whereas chelatable lead is significantly and linearly related to evidence of critical effect on hemoglobin synthesis in the bone marrow. Erythrocyte protoporphyrin and δ-aminolevulinic acid and coproporphyrin in urine are indicators of this effect. The dose-response concept provides a better way of viewing the relationship between blood lead and measures of adverse effect than do the classifications of “sensitivity,” “specificity,” “false negatives,” and “false positives,” which are often employed in the evaluation of screening tests. The doseresponse concept recognizes the uniqueness of the individual and the presence of susceptible and resistant individuals in heterogeneous population groups. With the dose-response concept, individuals may be identified as reactors or nonreactors, according to whether they exhibit a particular effect. Among the various indicators of lead's critical (or first) effect on hemoglobin synthesis, erythrocyte protoporphyrin potentially is the most practical for monitoring children at high risk for plumbism.