Prospective studies on physical activity in relation to the risk for hypertension are scant, particularly in women. This study aimed at finding out whether regular physical activity can reduce the risk of hypertension in both men and women, and in subjects with and without overweight. We prospectively followed 8302 Finnish men and 9139 women aged 25 to 64 years without a history of antihypertensive drug use, coronary heart disease, stroke, and heart failure at baseline. Both single and joint associations of physical activity and body mass index with the risk of hypertension were examined using Cox proportional hazard models. During a mean followup of 11 years, there were 1600 incident cases of drug-treated hypertension. Multivariate-adjusted hazards ratios of hypertension associated with light, moderate, and high physical activity were 1.00, 0.63, and 0.59 in men (Ptrend<0.001), and 1.00, 0.82, and 0.71 in women (Ptrend=0.005), respectively. This association persisted both in subjects who were overweight and in those who were not. Multivariate-adjusted hazards ratios of hypertension based at different levels of body mass index (<25, 25 to 29.9, and > or =30) were 1.00, 1.18, and 1.66 for men (Ptrend<0.001), and 1.00, 1.24, and 1.32 for women (Ptrend=0.007), respectively. Further adjustment for baseline systolic blood pressure did not affect the protective effect associated with physical activity, but it weakened markedly the association between body mass index and hypertension. The present study indicates that regular physical activity and weight control can reduce the risk of hypertension. The protective effect of physical activity was observed in both sexes regardless of the level of obesity.