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Clinical disturbances of the circulating sodium concentration are both a cause and a consequence of cerebrovascular disease. We examined the relationship between serum sodium level and risk of stroke and major ischaemic heart disease in a prospective study of 7690 middle-aged males drawn from general practices in 24 British towns followed over a 9.5-year period.The mean serum sodium level was 141.5 mmol/l and 375 males on antihypertensive treatment were excluded from the analyses. A significant inverse trend was seen between serum sodium and risk of stroke up to 144 mmol/l; above this the risk of stroke was increased. Those with levels of 143–144 mmol/l showed over a 70% reduction in risk of stroke compared with those with levels of ≤140 mmol/l. The inverse relationship between sodium and stroke up to 144 mmol/l was seen in males with and without pre-existing ischaemic heart disease or stroke, in normotensives and untreated hypertensives, and in non-smokers and current smokers. A weak but significant inverse association was seen between serum sodium and diastolic but not systolic blood pressure. The association between serum sodium level and stroke remained significant after adjustment for diastolic blood pressure and other factors associated with stroke: age, smoking, social class, body mass index, physical activity, heavy drinking, presence of diabetes, blood glucose and pre-existing ischaemic heart disease. No association was seen between serum sodium level and risk of ischaemic heart disease after adjustment for other risk factors. All-cause and non-cardiovascular mortality were significantly increased at serum sodium levels of ≤138 mmol/l, probably due to an association between lung cancer and hyponatraemia.These findings suggest that sodium concentration may be related to risk of stroke even at levels of sodium usually regarded as normal.