Objective-The reasons for the relationship between inflammation-sensitive plasma proteins (ISPs) and incidence of cardiovascular diseases are poorly understood. This study explored the hypothesis that ISPs are associated with future hypertension and age-related blood pressure increase. Method and Results-Blood pressure and plasma levels of fibrinogen, alpha1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were determined in 2262 healthy men aged 35 to 50 years, initially without treatment for hypertension. The cohort was re-examined after 15.7 (+/-2.2) years. Incidence of hypertension and blood pressure increase was studied in relation to number of elevated proteins (ie, in the top quartile) at baseline. Among men without treatment for hypertension at follow-up, mean (+/-SD) increase in systolic blood pressure was 18.8+/-17, 19.2+/-17, 19.3+/-17, and 22.1+/-18 mmHg, respectively, for men with 0, 1, 2, and greater than or equal to3 elevated proteins (P for trend=0.02, adjusted for confounders). The corresponding values for pulse pressure increase was 15.5+/-14, 15.8+/-14, 17.4+/-14, and 17.8+/-15 mm Hg, respectively (P= 0.02). Incidence of hypertension (greater than or equal to160/95 mm Hg or treatment) and future blood pressure treatment showed similar associations with ISPs. Increase in diastolic blood pressure showed no association with ISPs. Conclusions-Plasma levels of ISPs are associated with a future increase in blood pressure. This could contribute to the relationship between ISP levels and cardiovascular disease. (Arterioscler Thromb Vasc Biol. 2002;22:2054-2058.).