To examine the long-term effects of weight loss and dietary sodium reduction on the incidence of hypertension, we studied 181 men and women who participated in the Trials of Hypertension Prevention, phase 1, in Baltimore, Md. At baseline (1987 to 1988), subjects were 30 to 54 years old and had a diastolic blood pressure (BP) of 80 to 89 mm Hg and systolic BP <160 mm Hg. They were randomly assigned to one of two 18-month lifestyle modification interventions aimed at either weight loss or dietary sodium reduction or to a usual care control group. At the posttrial follow-up (1994 to 1995), BP was measured by blinded observers who used a random-zero sphygmomanometer. Incident hypertension was defined as systolic BP > or =160 mm Hg and/or diastolic BP > or =90 mm Hg and/or treatment with antihypertensive medication during follow-up. Body weight and urinary sodium were not significantly different among the groups at the posttrial follow-up. After 7 years of follow-up, the incidence of hypertension was 18.9% in the weight loss group and 40.5% in its control group and 22.4% in the sodium reduction group and 32.9% in its control group. In logistic regression analysis adjusted for baseline age, gender, race, physical activity, alcohol consumption, education, body weight, systolic BP, and urinary sodium excretion, the odds of hypertension was reduced by 77% (odds ratio 0.23; 95% confidence interval 0.07 to 0.76; P=0.02) in the weight loss group and by 35% (odds ratio 0.65; 95% confidence interval 0.25 to 1.69; P=0.37) in the sodium reduction group compared with their control groups. These results indicate that lifestyle modification such as weight loss may be effective in long-term primary prevention of hypertension.