Isolated systolic hypertension (ISH), defined as systolic blood pressure of 160 mm Hg or greater when the diastolic pressure is less than 95 mm Hg, is a common form of hypertension among the elderly. We collected incidence and prevalence data on ISH and evaluated several potential factors for its occurrence in the Framingham Heart Study during 16 biennial examinations. The factors evaluated were age, sex, all components of the blood pressure (systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure), Metropolitan relative weight, serum cholesterol level, serum uric acid level, cigarette smoking, ventricular heart rate, glucose intolerance, and hematocrit. The population at risk (1687 men and 1992 women) were those members of the Framingham cohort with a systolic blood pressure less than 160 mm Hg in the first four biennial examinations. Results showed ISH in 14.4% of the men and 22.8% of the women. Cumulative incidence rates were 418 per 1000 in men and 533 per 1000 in women. Significant risk factors for ISH were age, sex, all components of the blood pressure, and increased relative weight in women. We conclude that ISH is a highly prevalent disorder. Its major determinants are age, sex, increasing levels of blood pressure, and obesity in women.