Cocaine- and amphetamine-regulated transcript (CART) peptide is a novel neuropeptide involved in feeding, drug reward, and stress. We hypothesized that the polymorphism of CART gene might be related with susceptibility to neuropsychiatric diseases such as alcoholism, bipolar disorder, and schizophrenia. The polymorphism (rs2239670) in intron 1 was selected for study among other single nucleotide polymorphisms (SNPs) located at the area of CART gene, because it had not been tested until to date. The study included patients of alcoholism (100), bipolar disorder (76) and schizophrenia (169) from the Korean population. Healthy controls for bipolar disorder and schizophrenia consisted of 333 individuals. For alcoholism, both patient group and control subjects included only male. The restriction fragment length polymorphism (RFLP) using the AvaII restriction enzyme was designed to analyze the selected SNP. The distribution of GG, GA, and AA genotypes in the 333 controls was 50.2, 41.1, and 8.7%, respectively. The frequency of G and A alleles in the 333 controls was 70.7 and 29.3%, respectively. The distribution of genotype and allele frequencies of the AvaII polymorphism showed a significant difference between alcoholism and controls (P = 0.037 and P = 0.044). However, the AvaII polymorphism of the CART gene did not show association with bipolar disorder and schizophrenia. In conclusion, we report for the first time that the AvaII polymorphism (rs2239670) in intron 1 of the CART gene is associated with alcoholism in the Korean male population.