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Lungs exposed to particulate debris may be damaged by proteolytic enzymes during phagocytosis. Damage is worse if patients are deficient in α1-antitrypsin (A1AT), which helps neutralise these enzymes. We investigated the possibility that A1AT deficiency contributes to aseptic loosening following total hip replacement (THR) when wear particles are phagocytosed.A1AT level and phenotype were measured in patients attending for revision THR within 15 years of implantation. Periprosthetic lysis was graded from radiographs by three hip surgeons with an interest in revision, blinded to history and A1AT results. Patients were grouped according to presence of high or low levels of lysis radiologically. Mean A1AT levels were calculated for the two groups.17 patients were recruited, mean age 69.5, mean interval between surgery and onset of pain 8.3 years (2-12). Two were heterozygotes for the less active S form of A1AT and therefore mildly deficient. Time to onset of pain in both was 12 years. Radiographs were available for 12 patients. Combining the results for all reviewers the probability of a difference in the level of A1AT between the high and low lysis groups reached statistical significance (p=0.008). For all reviewers, the mean A1AT level in their high lysis group was raised and greater than that of their low lysis group. Both A1ATdeficient patients were classified as high lysis by all reviewers.The incidence of A1AT deficiency is only marginally higher in this group than in the general population therefore A1AT deficiency is unlikely to be a common cause of failure of hip replacements. Elevated levels of A1AT in the presence of lysis suggest that A1AT may play a role in the aetiology of aseptic loosening. A1AT-deficient patients may be at increased risk of osteolysis. Further work is needed to evaluate this and to assess vulnerability of A1AT-deficient patients to lysis.