Individual variation in drug response is considered to have multiple origins arising from interactions among susceptible genes and environmental factors. A total of 726 hypertensive patients who took benazepril 10 mg once a day for 15 days and their families from Huoqiu county of Anhui Province, China, were used to study the association between D919G polymorphism of methionine synthase (MTR) gene and the antihypertensive effect of this angiotensin-converting enzyme inhibitor. Compared to the 919D allele, both population-based ( P=0.010) and family-based association tests (additive model P=0.018, dominant model P=0.025) demonstrated that the 919G allele was associated with a significantly less diastolic blood pressure reduction. No significant association was found between the extent of systolic blood pressure reduction and benazepril therapy. Our finding suggests that the D919G polymorphism of the MTR gene may be a useful genetic marker to predict the antihypertensive effect of short-term benazepril therapy in hypertensive patients of Anhui Province, China.