Matrix metalloproteinases (MMPs) are enzymes involved in the degradation of the extracellular matrix. MMP-2 and MMP-9 have been implicated in a variety of pathological conditions including cardiovascular and neoplastic diseases, and recent studies have shown that circulating concentrations of MMP-9 may be a marker helping in the diagnosis and prognosis of cardiovascular and neoplastic diseases. We investigated whether there is an association between plasma MMP-2 and MMP-9 activities and the concentrations of lead in whole blood (blood Pb) or plasma (plasma Pb) from 40 lead-exposed persons (22 men and 18 women). Plasma Pb was determined by inductively coupled plasma mass spectrometry (ICP-MS) and blood Pb by graphite furnace atomic absorption spectrometry (GF-AAS). Plasma MMP-2 and MMP-9 activities were measured by gelatin zymography. We found a significant correlation between pro-MMP-9 activity in plasma and blood Pb (r=0.454; P=0.003), and between pro-MMP-9 activity in plasma and plasma Pb (r=0.312; P=0.049). No significant correlations were found between blood Pb or plasma Pb and plasma MMP-2. The association between pro-MMP-9 activity in plasma and both blood Pb and plasma Pb concentrations suggests a mechanism through which low lead exposure may increase the susceptibility to cardiovascular and neoplastic diseases. A causal relationship, however, remains to be proved.