Compared to office measurements, ambulatory monitoring is a more accurate method of blood pressure (BP) characterization and may therefore be useful in a genetics study of hypertension. We studied the relation between the M235T polymorphism of the angiotensinogen gene and hypertension using office and ambulatory (BP) measurements. We enrolled untreated subjects (33 men and 17 women) who were referred for evaluation of office BP >140/90 mm Hg on at least two separate occasions. The M235T genotypes of the angiotensinogen gene were determined by polymerase chain reaction (PCR) amplification of DNA extracted from peripheral blood leukocytes and digested with BSTU1. The distribution of the genotypes were MM = 0.22, MT = 0.44, TT = 0.34. Based on office measurements, a significant difference in diastolic blood pressure (BP) was detected only between the TT and the MT genotype subjects (office BP: MM = 150 +/- 25/97 +/- 13 mm Hg, MT = 147 +/- 23/ 95 +/- 13 mm Hg, TT = 161 +/- 25/104 +/- 15 mm Hg). By contrast, with ambulatory BP monitoring, both systolic and diastolic blood pressures were significant higher in TT versus MM and MT (ambulatory BP, MM = 138 +/- 10/88 +/- 9 mm Hg, MT = 141 +/- 15/89 +/- 11 mm Hg, TT = 152 +/- 18/97 +/- 12 mm Hg). Covariate analysis revealed an independent relationship between the M235T genotype and systolic, diastolic, and mean ambulatory BP. Ambulatory monitoring improved the analytic power of our study and allowed detection of a clear and consistent relationship between angiotensinogen polymorphism and hypertension with a relatively small sample size.