The British Regional Heart Study seeks to explain the geographic variations in cardiovascular disease in Great Britain. A strong geographic gradient in the risk of a major ischaemic heart disease (IHD) event was found in 7735 middle-aged men who were followed up for 6.5 years. Regardless of where they were born, men examined in Scotland experienced the highest IHD risk, while those examined in the South of England had the lowest. The place of examination (ie, residence) was a more important determinant of the risk of a major IHD event than the place of birth. It seems unlikely that the geographic differences in IHD risk among middle-aged British men can be directly explained by their genetic inheritance or by their prenatal and postnatal diet.