Inorganic lead (Pb) is able to modulate the immune response even at low to moderate exposure levels. It inhibits in vitro and in vivo activities of neutrophil leucocytes and influences their blood count in humans. Neutrophil functions are governed by a number of cytokines. Pb has been shown to affect leukocyte production of some of these cytokines in vitro. The objective of this study is to assess serum tumor necrosis factor-alpha (TNF-alpha) and granulocyte colony-stimulating factor (G-CSF) levels of thirty-three male lead-exposed (E) workers at a lead recycling plant as compared with twenty-eight male non-exposed (NE) workers at a food processing plant, whose current smoking habit was known. Serum TNF-alpha and G-CSF levels were measured by a quantitative sandwich enzyme immunoassay. Blood lead levels (Pb-B) were significantly higher in E (geometric mean (GM) 30.7 microg/dl, GSD 1.7; min-max: 9.1-81.6 microg/dl) workers than controls (GM 3.6 microg/dl, GSD 1.7; min-max: 1.0-11.0 microg/dl). E workers had significantly higher serum TNF-alpha (median: 107.1; min-max: 11.1-623.0 pg/ml) and G-CSF levels (median: 53.0, min-max: 31.1-197.0 pg/ml) than NE workers (TNF-alpha: median: 12.0; min-max: 9.4-18.8 pg/ml; G-CSF: median: 34.3, min-max: 25.1-52.2 pg/ml). In particular, the TNF-alpha level was shown to be significantly influenced by lead exposure and smoking habit, as well as by interaction between these two factors. Both serum TNF-alpha and G-CSF levels were correlated with Pb-B and absolute neutrophil count. This study is the first to detect higher serum levels of G-CSF in E over NE workers. Our data confirm that exposure to low to medium doses of lead may interfere in the complex cytokine network involved in inflammation, especially in workers who are current smokers.