We test the hypothesis that chronic lead (Pb) exposure may be associated with an inability to maintain an adequate serum erythropoietin (EPO) concentration. From a longitudinal study of Pb exposure and infant and childhood development, we measured blood Pb (BPb) and serum EPO concentrations serially at ages 4.5, 6.5, 9.5, and 12 and tibia (cortical) Pb concentration at age 12. Pb-exposed children aged 4.5 and 6.5 produced increased concentrations of EPO to maintain normal Hgb concentrations. EPO production declined between ages 4.5 and 6.5. At ages 9.5 and 12, further diminution of the association was found. No association was found between tibia Pb and EPO. The continued decline in the slope of the relationship between EPO and BPb with age, after adjustment for hemoglobin, implies a gradually decreasing capacity to produce EPO.