The European standardized method for measuring porphobilinogen synthase (PBGS, EC 4.2.1.24) activity in peripheral erythrocytes is widely used in epidemiological studies of low-level Pb absorption. We have modified it to include activation with dithiothreitol (DTT). In children with concentrations of Pb in whole blood ranging from 0.29 to 1.93 mumol/L, we found the following statistically significant correlations (r): blood Pb vs nonactivated PBGS activity = -0.773 (p less than 0.005); blood Pb vs DTT-activated PBGS activity = -0.265 (p less than 0.005); blood Pb vs the ratio of DTT-activated/nonactivated PBGS activity = +0.818 (p less than 0.005). At a DTT-activated/nonactivated PBGS activity ratio of 1, which indicates no Pb-dependent inhibition of PBGS, a corresponding blood Pb concentration of 0.24 mumol/L (50 micrograms/L) would be predicted. In individuals with hematological disorders, the DTT-activated/nonactivated ratio better predicted blood concentration of Pb than did the nonactivated PBGS activity, and largely compensated for the high variability in PBGS activity. We also describe techniques to minimize contamination by Zn and Pb and to stabilize enzyme activity during collection, transport, storage, and analysis of samples.