The mortality experience of 68,153 men, 35 to 64 years of age, over a period representing 482,658 person-years of observation during which 4,706 known deaths occurred is related to their cigarette smoking habits. The findings are compared to the several other prospective studies reported in recent years relating mortality to cigarette smoking. All studies are in essential agreement that cigarette smoking increases the risk for cancer of the mouth, larynx, esophagus, lung, kidney, and bladder. A few other tissue sites appear to carry increased risk of cancer as a result of cigarette smoking in one or another study but without unanimity. The risk gradient for lung cancer by age and amount of smoking increases in successive 10-year age groups to be maximal at 55 to 64 years in our study. Other diseases related to cigarette smoking in this and other prospective studies are gastric ulcer, emphysema, aneurysm, general arteriosclerosis, and arteriosclerotic heart disease. The latter is especially important because of the large number of deaths involved. The relative risk gradient for arteriosclerotic heart disease by age and amount of cigarette smoking was found to be maximum in the youngest age group comprising men 35 to 44 years of age and lessens with increasing age. Future studies should be directed toward identifying other variables with which cigarette smoking interacts in those individuals developing disease.