RATIONALE: Cigarette smoking is emerging as a strong risk factor in the otherwise unknown etiology of chronic inflammatory diseases. Whether the same applies also to smokeless tobacco remains unknown. Nicotine is a powerful modifier of the inflammatory response. By comparing risks associated with tobacco smoking and with smokeless tobacco, the role of nicotine in the development of chronic inflammation may be evaluated. OBJECTIVES: To assess and compare the risks of rheumatoid arthritis (RA), ulcerative colitis (UC), Crohn's disease (CD), sarcoidosis, and multiple sclerosis (MS) associated with cigarette smoking and with the use of Swedish moist snuff. METHODS: We performed a cohort study of 277,777 males within a cohort of Swedish construction workers who had provided information about tobacco use in 1978-1993. Cross-linkage to the nationwide Swedish Hospital Discharge Register provided information about the occurrence of RA, UC, CD, sarcoidosis, and MS through 2004. MEASUREMENTS AND MAIN RESULTS: Age-adjusted relative risks (RRs) associated with smoking and moist snuff, respectively, were estimated by Cox regression. Ever-smoking was associated with an increased risk for RA (RR, 2.1; 95% confidence interval [CI], 1.7-2.5), CD (RR, 1.5; 95% CI, 1.2-1.8), MS (RR, 1.9; 95% CI, 1.4-2.6), and UC (RR, 1.3; 95% CI, 1.1-1.5, confined to ex-smokers), and a decreased risk of sarcoidosis (RR, 0.5; 95% CI, 0.4-0.5). By contrast, ever-use of moist snuff, adjusted for smoking, was not associated with RA (RR, 1.0; 95% CI, 0.9-1.2), UC (RR, 1.1; 95% CI, 0.9-1.2), CD (RR, 0.9; 95% CI, 0.8-1.1), sarcoidosis (RR, 1.1; 95% CI, 0.8-1.5), or MS (RR, 1.0; 95% CI, 0.8-1.4). CONCLUSIONS: Smokeless tobacco does not increase the risk of chronic inflammatory diseases, suggesting that inhaled nonnicotinic components of cigarette smoke are more important than nicotine itself in the etiology of these diseases.