Hyperhomocysteinemia is associated with several cardiovascular disease risk factors including endothelial dysfunction and abnormalities of clotting functions, which are also common features of insulin resistance syndrome observed in hypertensive patients. Recent study has shown that acute hyperinsulinemia can lower plasma homocysteine concentrations in nondiabetic but not in type 2 diabetic individuals, indicating that insulin may regulate homocysteine metabolism. To investigate the relationships between plasma homocysteine concentration and insulin sensitivity, we studied 90 Chinese hypertensive patients and a group of control subjects (n = 86) matched for age, gender, and body mass index. Fasting plasma homocysteine levels, plasma lipoprotein concentrations, plasma glucose, and insulin responses to oral glucose tolerance tests (OGTT) were determined. The results showed that fasting plasma homocysteine concentrations were significantly higher in subjects with hypertension than in those with normotension (mean +/- SEM, 8.1 +/- 0.6 v 6.8 +/- 0.2 micromol/L; P < .05). Fasting plasma homocysteine levels correlated significantly with insulin secretion in response to OGTT even after adjustment for body mass index (P < .05) in hypertensive patients but not in normotensive individuals. However, fasting plasma homocysteine concentrations showed no correlations with steady-state plasma glucose concentration, a measurement of insulin sensitivity, during an insulin suppression test in groups of hypertensive (n = 42) and normotensive (n = 37) subjects. When the steady-state plasma glucose concentrations were divided into three tertiles, fasting plasma homocysteine concentrations showed no difference across these three groups in either hypertensive patients (8.6 +/- 0.5 v 7.2 +/- 0.5 v 8.4 +/- 0.6 micromol/L; P = .148) or normotensive subjects (6.3 +/- 0.4 v 8.0 +/- 0.8 v 7.0 +/- 0.8 micromol/L; P = .199). In conclusion, hypertensive Chinese subjects had higher fasting plasma homocysteine concentrations and a higher degree of insulin resistance when compared to a group of age-, gender-, and body mass index-matched normotensive individuals. Fasting plasma homocysteine levels were associated with insulin response to OGTT in hypertensives but not in normotensives. No correlation was observed between the degree of insulin resistance and plasma homocysteine levels in either the hypertensive or the normotensive group. The role of insulin in homocysteine metabolism deserves further investigation.