Investigating initiation of smoking behavior and factors involved in developing nicotine dependence is an important health issue worldwide. Various environmental, psychological and genetic risk factors are studies in the background of this complex behavior. The self-medication hypothesis may account for the increased prevalence of smoking behavior and more pronounced nicotine dependence among psychiatric patients. The present study investigates smoking habit and dependence measures in 133 Caucasian patients diagnosed with major depression. Investigated categorical endophenotypes included of smoking behavior included non-smokers who never smoked (1), non-smokers who smoked previously (2), occasional present smokers (3), and regular present smokers (4). Dimensional endophenotypes of nicotine addiction have been characterized by Hungarian adaptations of the Hooked on Nicotine Checklist and the Fagerström Test for Nicotine Dependence. Polymorphic regions of the dopaminergic system have been included as candidate genetic factors including the repeat polymorphism in the III. Exon of the DRD4 (DRD4 VNTR), two promoter SNPs of this gene (-521 CT and -616CG), as well as the repeat polymorphism of the dopamine transporter (DAT VNTR) polymorphism and the Val/Met polymorphism of the catechol-O-methyltransferase (COMT) gene. No significant difference was found between the genotype distributions in the four categories of smoking behavior. However, a significant association is reported with nicotine addiction of patients with major depression using the dimensional approach: patients with the C allele showed lower average scores on the Nicotine Checklist (CC or CT: mean score = 6.8 +/- 3.4) as compared to those without the C allele (IT: mean score = 10.l +/- 2.5), these differences were significant (p = 0.003).