Alpha-1- antitrypsin (AAT) is a major plasma protein, being the predominant component of the alpha 1 globulin band seen on classical serum electrophoresis. AAT is a protease inhibitor that protects lung parenchyma from destruction by neutrophil elastase. When AAT is deficient, lung tissue is slowly destroyed, ultimately leading to pulmonary emphysema, and death.The gene locus for AAT is located on chromosome 14q 32.1. The 12.2 Kb AAT gene is comprised of seven exons. The AAT protein is extremely pleomorphic and > 90 variants have been identified. The most common type M, consists of at least six subtypes, all characterized by normal serum AAT. The Z and S variants are associated with AAT deficiency. The issue of whether the Z and S alleles are risk factors for chronic obstructive pulmonary disease (COPD) in the heterozygous state remains controversial.Tradionally, the characterization of the different AAT alleles has been carried out using iso-electric focusing (IEF) of serum.. Recently, the availability of techniques based on the polymerase chain reaction (PCR) permits the analysis of AAT variability at the gene level.The aim of the present study is to throw some light on the genetic bases of COPD, to clarify the role of AAT genotypes as a risk factor for development of COPD and to correlate AAT genotypes with serum AAT concentrations and respiratory function tests.This study was conducted on 44 subjects divided into the following groups:Group I: Twenty-four patients with documented COPD, all patients were subjected to respiratory function tests. Obstructed patients were those who had FEV1/FVC < 70%.Group II: Ten chronic heavy cigarette smokers without airway obstruction. Members of this group were clinically assessed and were subjected to pulmonary function tests.Group III: Ten non-smokers with normal pulmonary function test. Members of group II and III where those who had FEV1/FVC> 70%. Subjects for this study completed an interviewer administrated questionaire regarding smoking history, occupational exposure to dust and fumes and respiratory symptoms. In addition, they were subjected to thorough clinical examination.Studied subjects were subjected to the following investigations:1)Respiratory function tests. 2) Serum AAT level by immuno-nephelometery.3) AAT genotyping by a line probe assay using amplified DNA by polymerase chain reaction.This work revealed that MZ heterozygotes had reduced lung function compared with MM individuals within the COPD patients. Thus, it seems that the 25% decrease in AAT concentrations attributable to the MZ genotype affected lung function only in those who are susceptible to COPD.So, if AAT genotyping was performed early in life, carriers of the Z allele would be recognized. Those individuals being more prone to develop COPD, might benefit from living in a healthy environment away from tobacco smoke, air pollution and recurrent chest infections.