Objective To investigate whether high levels of serum immunoglobulin A-alpha1 proteinase inhibitor (IgA-alpha1PI) complexes are primarily, associated with cigarette smoking or the rheumatoid arthritis (RA) disease process itself. Methods A case-control study consisting of 231 RA cases and 83 healthy hospital workers. A smoking history was taken for the study groups. The serum IgA-alpha1PI complex levels (arbitrary units, au) were determined using a sandwich ELISA. Erythrocyte we sedimentation rate (ESR) and rheumatoid factor (RF) measurements were recorded in each of the RA cases. The serum complex levels were compared between RA cases and controls matched for smoking history and between smokers and non-smokers in the RA cases and controls. Results Mean serum IgA-alpha1PI complex levels were significantly higher in RA current smokers than in non-smoking RA patients (17.4 v 11.9 a. u., p=0.0001). Similarly, mean serum complex levels were significantly higher in control current smokers than control non-smokers (18.8 v 11.5 a.u., p=0.003). Seropositive RA cases had significantly higher complex levels than seronegative cases. Patients with erosive disease had higher levels than non-erosive patients, although significance was lost after correction for current smoking and RF positivity. There was an association between ESR and serum IgA-alpha1PI complex levels which was independent of current smoking. Overall, there was no significant difference in complex levels between RA cases and controls after correction for current smoking. Conclusion Raised serum IgA-alpha1PI complex levels are associated with current smoking in both RA and healthy controls. ESR levels in RA patients are also associated with serum complex levels independently of current smoking. Our data suggest that high IgA-alphaIPI complex levels can be generated either as a result of current smoking, or by an active disease process in RA patients.