Smoking is rare in patients with ulcerative colitis (UC). Onsets are common after stopping smoking. Several observations suggest possible immunologic mechanisms in UC. As smoking has an immunosuppressive effect, a possible role of smoking in UC could be immunosuppression. In this study an analogous hypothesis was investigated by studying smoking habits in patients with systemic lupus erythematosus (SLE), an inflammatory multisystemic disease of unknown etiology, characterized by disturbances in cellular and humoral immunity. At onset, 23 of 56 patients were smokers and 2 probable smokers. Few were ex-smokers. The patients were matched for age, sex, and geographic vicinity, and multiple relative risks were calculated. No correlation could be found between smoking/ex-smoking and SLE either at diagnosis or at interview, and no resemblance in habit to patients with UC was found. The present study provides no evidence that the immunosuppressive effect of smoking is sufficient to influence the clinical course of SLE and therefore by analogy does not support an immunosuppressive explanation of the possible protective effect of smoking in UC.