BACKGROUND: Cigarette smoking has been linked to thyroid disease, although studies of this problem have not shown consistent affects, with some studies linking smoking to increased thyroid hormone levels, and others to decreased thyroid hormone levels. METHODS: We performed a secondary analysis of information collected from 4462 Vietnam-era male US Army veterans aged 31-49 years who participated in the Vietnam Experience Study in 1985-1986. The study group consisted of 1962 current smokers and 2406 current non-smokers who had no thyroid abnormalities on physical examination, no current use of thyroid medicine, and no history of thyroid disease. RESULTS: We found that current smokers have higher thyroxine levels and lower thyroid stimulating hormone levels than never smokers and former smokers. The higher thyroxine levels that we detected in smokers, compared to non-smokers, diminished when we controlled for thyroxine-binding globulin and testosterone. We also found that heavy smokers had a smaller increase in thyroxine levels than did light smokers, when compared to non-smokers. CONCLUSIONS: Our findings suggest at least two distinct mechanisms for the effect of tobacco smoke on thyroid function; one related to higher levels of thyroxine-binding globulin and testosterone among smokers compared to non-smokers and another related to higher levels of thyrotoxins in tobacco smoke in heavy smokers compared to light and moderate smokers.