The genes coding for the protease inhibitors alpha 1-antitrypsin (A1AT) and alpha 1-antichymotrypsin (A1ACT) were analysed by Southern blot in patients with rheumatoid arthritis, psoriatic arthritis, psoriasis without arthritis, polymyalgia rheumatica and generalized osteoarthritis. The probe/restriction enzyme combinations used were the 4.6 kb 5' fragment of the A1AT gene with the Sst I enzyme, the 6.5 kb 3' fragment of the same gene with Taq I and the 3.4 kb fragment of A1ACT with Taq I. The frequency of homozygous genotype for the 5.8 kb A1ACT band was increased in osteoarthritis (62.8% versus 36.8%, P = 0.01, relative risk = 2.9, aetiological fraction = 0.41). No other disease association was found with any marker. This suggests that the A1ACT gene may influence susceptibility to generalized osteoarthritis.