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OBJECTIVE: To determine the body mass index associated with the lowest morbidity and mortality. DESIGN: Prospective study of a male cohort. SETTING: One general practice in each of 24 British towns. SUBJECTS: 7735 men aged 40-59 years at screening. MAIN OUTCOME MEASURES: All cause death rate, heart attacks, and stroke (fatal and non-fatal) and development of diabetes, or any of these outcomes (combined end point) over an average follow up of 14.8 years. RESULTS: There were 1271 deaths from all causes, 974 heart attacks, 290 strokes, and 245 new cases of diabetes mellitus. All cause mortality was increased only in men with a body mass index (kg/m2) < 20 and in men with an index > or = 30. However, risk of cardiovascular death, heart attack, and diabetes increased progressively from an index of < 20 even after age, smoking, social class, alcohol consumption, and physical activity were adjusted for. For the combined end point the lowest risks were seen for an index of 20.0-23.9. In never smokers and former smokers, deaths from any cause rose progressively from an index of 20.0-21.9 and for the combined end point, from 20.0-23.9. Age adjusted levels of a wide range of cardiovascular risk factors rose or fell progressively from an index < 20. CONCLUSION: A healthy body mass index in these middle aged British men seems to be about 22.