Chronic sub-clinical inflammation observed in hypertension plays a prominent role in the progression of atherosclerosis. Accumulating evidence suggests that homocysteine (Hcy) can cause inflammation. The aim of this study was to compare the predictive utility of Hcy and lipid measures as determinants of inflammation in hypertensive patients. We studied a group of 100 patients (45.0+/-12.2 years old) with essential hypertension and a control group of 40 healthy volunteers (44.0+/-8.7 years old). We found that plasma total Hcy (tHcy), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and C-reactive protein (CRP) were significantly higher in hypertensive patients compared with the control group. The subgroup of hypertensive patients with obesity had higher levels of TNF-alpha (p<0.001), IL-6 (p<0.01), and tHcy (p=0.063), compared with the subgroup of hypertensive patients without obesity. The subgroup of patients with a history of myocardial infarction or stroke had significantly higher levels of tHcy, TNF-alpha, IL-6, and CRP compared to patients with a negative history of vascular events. In the group of hypertensive patients, a strong positive correlation between tHcy and TNF-alpha was observed (r=0.48; p<0.001). In contrast, no correlation was observed between TNF-alpha and any of the lipid measures. In multivariate regression analysis tHcy, but not lipids, was an independent predictor of TNF-alpha. In conclusion, our findings show that plasma tHcy is a determinant of TNF-alpha in hypertension and that obesity or a history of vascular events aggravates inflammation in patients with hypertension. A positive correlation between Hcy and TNF-alpha suggests a mechanism underlying the pro-atherogenic properties of Hcy.