Studies suggest that homocysteine may elevate blood pressure and increase the risk of hypertension. The association of homocysteine with blood pressure and with the risk of hypertension was investigated using cross-sectional data from the Third National Health and Nutrition Examination Survey (1998-1994). Homocysteine had an independent positive association with blood pressure after adjusting for cardiovascular risk factors. A 1 standard deviation ( approximately 5 micro mol/liter) increase in homocysteine was associated with increases in diastolic and systolic blood pressure of 0.5 and 0.7 mmHg, respectively, in men and of 0.7 and 1.2 mmHg in women. Similarly, higher levels of homocysteine were associated with an increased risk of hypertension. In a comparison of the highest and lowest quintiles of homocysteine, women had a threefold increase in the risk of hypertension (95% confidence interval (CI): 1.7, 5.4), and men had a twofold increase (95% CI: 0.7, 5.1). In light of the homocysteine-blood pressure association, the association of homocysteine with prevalent cardiovascular disease was examined with and without adjusting for blood pressure. The results support a mediating role for blood pressure in women and suggest that the full effect of homocysteine on cardiovascular risk may be underestimated when blood pressure is adjusted.