Risk of clinical relapse among cigarette smokers and nonsmokers was examined in a cohort of 74 adult Crohn's disease (CD) patients who were identified and followed at monthly intervals for six months. We measured clinical activity by a weighted symptom index used previously. Relapse at any point during the study was defined by the index score exceeding 150. Approximately 50% of nonsmokers experienced clinical relapse during the study period. Current smokers experienced a relapse risk 1.6 times that of nonsmokers (P less than .01). The risk estimates correspond to mean overall clinical activity scores of 142 +/- 34 for smokers compared to 119 +/- 26 for nonsmokers. Adjustment for confounding effects did not substantially alter the association shown between cigarette use and clinical relapse. We observed no increase in the likelihood of relapse among former smokers. The statistically significant finding that current smoking increases the risk of relapse for CD patients is of clinical importance, given the high prevalence of smoking (42%) among CD patients in this sample.