Two restriction fragment length polymorphisms (RFLPs) of the flanking sequence of the alpha 1-antitrypsin (AAT) gene, detected with the restriction enzymes HindIII and TaqI, have been reported to occur more commonly in patients with chronic obstructive airways disease (COAD). Their frequencies were investigated in 20 Caucasian families with a family history of COAD and in 140 unrelated COAD patients none of whom had AAT deficiency. The HindIII polymorphism was present in six index cases of 20 families (p = 0.0015) and 14 of the unrelated patients (p = 0.061) compared with one of 60 healthy unrelated controls. The TaqI polymorphism was present in five of 101 healthy unrelated controls and in three index cases of the 20 families. In the unrelated patient group 28 of 140 had the polymorphism (chi 2 = 10.01, p = 0.0016) and corresponds to a mean log odds ratio of 1.56 (95 per cent confidence limits of 0.58-2.56). The polymorphisms occurred independently of each other and were not associated with AAT deficiency in the basal state.