Although Buerger's disease is known to be closely related to smoking, no objective analysis of the smoke-associated problems has been performed. In this study, cotinine, the major metabolite of nicotine, was used as a sensitive marker to measure levels of active smoking and the exposure of nonsmokers to tobacco smoke because it has a relatively long half-life and because cotinine levels can be determined by noninvasive means in urine. According to urinary cotinine levels, 40 patients with Buerger's disease were classified as (1) smokers: those with urinary cotinine levels above 50 ng/mg creatinine; (2) passive smokers: those with levels between 10 and 50 ng/mg creatinine; and (3) nonsmokers who did not experience noticeable passive smoking: those with levels below 10 ng/mg creatinine. There were 10 smokers, 9 passive smokers, and 21 nonsmokers. The course of the disease, after the initial treatment at our hospital, was studied retrospectively. Seven of the 10 smokers, none of the 9 passive smokers, and 4 of the 21 nonsmokers experienced aggravation of the disease. Of the four nonsmokers who experienced aggravation, three had still been smokers and one had been exposed to tobacco smoke in the workplace at the time of relapse. There was a significant difference in the aggravation rate between the smokers' group and the other two groups. Among the smokers, the seven patients whose conditions worsened showed significantly higher cotinine levels than the three remaining patients who were in the stage of remission.(ABSTRACT TRUNCATED AT 250 WORDS)