Two enzymes, chymase and angiotensin converting enzyme (ACE), are involved in the production of angiotensin II. Our previous study revealed the male-specific effect of the ACE DD genotype on the risk for hypertension, but the genetic role of chymase remains unclear. In the present study, we report the results of an association study involving 1,046 subjects recruited from a general population in Ohasama, a rural community in the northern part of Japan. In addition to casual blood pressure (casual BP) measurement, home BP measurements were obtained from all participants. There were no differences in either home or casual BP values according to G3255A polymorphism of the mast cell chymase gene (MCC). HDL cholesterol level was significantly higher among carriers of the A3255 allele (p<0.04). After adjustment for confounding factors, the A3255 allele was still shown to have an effect on HDL cholesterol metabolism (p<0.03). Multiple regression analysis showed that MCC polymorphism was significantly and independently related to serum HDL cholesterol level. In conclusion, G3255A polymorphism of MCC is not directly associated with blood pressure but may modulate the prevalence of hypertensive complications via alteration of lipid metabolism.