The present case-control study was conducted to investigate the relationship 
between smoking and rheumatoid arthritis, and to investigate formally the 
interaction between sex, smoking, and risk for developing rheumatoid arthritis. 
The study was performed in the Central District of Finland. Cases were patients 
with rheumatoid arthritis and the control group was a random sample of the 
general population. Logistic regression models were used to evaluate the effect 
of smoking on risk for rheumatoid arthritis, after adjusting for the effects of 
age, education, body mass index, and indices of general health and pain. 
Overall, 1095 patients with rheumatoid arthritis and 1530 control individuals 
were included. Patients were older, less well educated, more disabled, and had 
poorer levels of general health as compared with control individuals (all P < 
0.01). Preliminary analyses revealed the presence of substantial statistical 
interaction between smoking and sex (P < 0.001). In separate multivariable 
analyses, past history of smoking was associated with increased risk for 
rheumatoid arthritis overall in men (odds ratio 2.0, 95% confidence interval 
1.2-3.2) but not in women. Among men, this effect was seen only for rheumatoid 
factor-positive rheumatoid arthritis. There were significant interactions 
between smoking and age among women but not among men. We conclude that sex is a 
biologic effect modifier in the association between smoking and rheumatoid 
arthritis. The role of menopause in the etiology of rheumatoid arthritis merits 
further research.