Individuals homozygous for the autosomal recessive disorder CF are known to have low blood pressure, thought to be caused by greatly increased sweat salt loss. We examined whether carriers of the CF gene also have low blood pressure. Our pilot studies had suggested an effect limited to females, leading to 2 further studies in white females. In the first, blood pressure was measured in 232 known CF mutation carriers and compared with 246 mutation-negative control subjects. The carriers showed a significantly lower rate of increase in systolic blood pressure with age than the controls, especially after age 50 (3.5% per decade compared with 5.4% per decade, P=0.010). In a small substudy, sweat sodium and chloride levels were highest in those CF carriers with the lowest blood pressures. In the second study, CF carrier status was investigated in 563 normotensive females and in 607 women with essential hypertension diagnosed to test whether a lower incidence of carriers in the hypertensives suggested a protective effect. Twenty-five of the normotensives (4.4%) were carriers compared with 21 (3.5%) of the hypertensive group (P=0.45). Older CF carrier females had lower systolic and diastolic pressures than matched control subjects, with a tendency for blood pressure to increase less with age. This could result in significant reduction in stroke and heart disease. The effect on blood pressure is insufficient to prevent hypertension, though it remains conceivable that the severity might be ameliorated in carriers.