Adrenoceptors (ARs) consist of nine subtypes, which are involved in a wide spectrum of physiological functions and are the site of action for a considerable percentage of currently prescribed therapeutics. All AR subtypes (except alpha(1D)) can be polymorphic because of the genetic variations in the coding and non-coding regions. Sixteen sequence variations were identified in a-adrenergic 2A (ADRA2A) gene. Among them. ADRA2A C1291G polymorphism is one of the most important polymorphisms. which plays a major role in regulating neurotransmitter release, blood pressure, lipolysis. insulin secretion, and platelet aggregation. A C-G transversion results in an Mspl restriction frament length polymorphism located at 1291 bp upstream of the origin of transcription. Because Medline search showed no study showing the allelic frequencies, and no information is available on inter-individual variability of ADRA2A C1291G polymorphism in Turkish Population, we genotyped 203 healthy Turkish subjects. Because of large genetic variation of the polymorphism, we aimed to find out the distribution of C1291G polymorphism in Turkish population. Furthermore. we evaluated the possible association between the C1291G polymorphism in the ADRA2A receptor gene and smoking. The frequencies For the 1291C and 1291G alleles were 64%, and 36%, respectively. The genotype frequencies for C1291, C1291G, and G1291G were 35.5%, 57.6%, and 6.9%, respectively, in Turkish population. The allelic Frequencies (1291C and 1291G) and G1291G homozygous variant genotype were similar to those reported in different Caucasian populations;, however, C1291C and C1291G genotypes were different. We also observed that the frequency of the G allele was slightly higher in smoker subjects and lower among controls. The A DRA2A G allele may play a role in the predisposition to smoking. There is a need for expanding genotype and haplotype studies because of its importance in various physiological disorders and to confirm the association of this polymorphism with smoking. Toxicology and Industrial Health 2008; 24: 171-176.