PURPOSE: The interactive effects of genetic polymorphisms of cytochrome P4502E1 (CYP2E1) & N-acetyltransferase 1 (NAT1) and smoking on lung cancer development were evaluated in hospital based case-control study. MATERIALS AND METHODS: Male lung cancer patients (N= 157) and the male patients with no present or previous history of systemic illnesses who visited the urology department (N=138) were recruited (1998-1999). CYP2E1 & NAT1 genotypes were determined by PCR-RFLP method using RsaI and MboII digestion, respectively. RESULTS: CYP2E1 c2 or NAT1 *10 allele did not increased the risk of lung cancer. Heavy smokers (35