The joint effects of tobacco use and body mass on mortality have not been well characterized, although evidence regarding the effect of smoking on the association between body mass and mortality is accumulating. To study the joint effects of these important risk factors, the authors conducted a prospective cohort study of 148,173 men and women aged > or =35 years in Mumbai, India. Subjects were recruited during 1991-1997 and then followed for approximately 5-6 years (1997-2003). During 774,129 person-years of follow-up, 13,261 deaths were observed. Tobacco use increased the risk of death across different categories of body mass, with particularly high risks being observed in extreme body mass categories. Among men, obese smokers and obese never users of tobacco were at 56% and 34% increased risks of death, respectively, compared with overweight never users of tobacco. Similarly, at highest risk were extremely thin males who smoked bidis (relative risk = 3.45) or cigarettes (relative risk = 3.32). Body mass and all forms of tobacco use had independent as well as multiplicative joint effects on mortality risk. Tobacco use and undernutrition are serious problems in India. The current study indicates that obesity may emerge as a serious public health problem with which tobacco use may interact.