OBJECTIVE: The objective of this study was to study the impact of work-related exposure to mainly arsenic and lead versus smoking in primary smelter workers developing lung cancer. METHODS: In a cohort of 3979 primary smelter workers, 46 subjects had contracted respiratory malignancies. They were compared with 141 age-matched male referents by conditional logistic regression analysis. RESULTS: Cases showed a significantly higher smoking rate as compared with referents: odds ratio (OR) = 4.0; 95% confidence interval (CI) = 1.6-10.1; P = 0.003. When restricted to smokers (33 cases, 63 referents), the cumulative air arsenic exposure index, but not the lead exposure indices, was significantly higher among the cases: OR = 1.07; 95% CI = 1.02-1.11; P = 0.005. CONCLUSIONS: Cumulative arsenic exposure and smoking were identified as risk factors for the development of lung cancer; lead exposure, however, was not.