Pyrimidine 5'-nucleotidase (P5N, EC 3.1.3.5) appears to be a sensitive index of exposure to low level lead. In 21 children 2 to 5 years old with blood leads of 7 to 80 micrograms/dl there was a negative linear correlation of blood lead and red cell P5N: r = -0.60 (P less than 0.01), Y = -0.11X + 12.3. In rats, the enzyme assay was quantitatively similar to that of the human. A treatment group of 12 rats received lead acetate, 36 mg/kg/day, of lead as 0.17 M lead acetate for 24 days. The blood lead of treated rats increased from the control value of 8.3 +/- 1.3 to 36.0 +/- 0.5 on day 24; P5N decreased from 18.3 +/- 0.8 units to 9.0 +/- 1.0 and was below control values at a blood lead of 25. There was a significant negative linear correlation of blood lead and P5N: r = -0.85; n = 17; P less than 0.001; Y = 0.34X + 20.9 that was independent of the correlationship with the reticulocytes. At these levels of blood lead and P5N there was no significant change in the hexokinase, hemoglobin or red cell count and no evidence of stippling.