In a 22-year followup of 3686 San Francisco longshoremen, the roles of physical activity, cigarette smoking habit, and systolic blood pressure level were evaluated independently in relation to risk of death from a broad range of diseases. Smoking pattern and blood pressure status were established in 1951 and job activity was assessed annually during the followup period. Lower levels of energy expenditure predicted increased risk of fatal heart attack and perhaps of stroke. Heavy cigarette smoking predicted increased risk of death from heart attack, cancer, chronic obstructive respiratory disease, and pneumonia. Higher levels of systolic blood pressure were associated with death from all cardiovascular diseases, diabetes mellitus, and cirrhosis. Tacit to these findings: sedentary living takes its toll largely through heart disease and stroke; the toxicity of cigarette smoking is associated with a broader range of diseases, including heart attack, cancer, and respiratory disease; and higher level of blood pressure related to an even broader range of cardiovascular disease than either of the other characteristics studied.