To investigate whether the polymorphisms in the angiotensin-converting enzyme and angiotensinogen genes are associated with hypertension, we carried out a case-control study of 508 hypertensive and 523 control subjects randomly selected from the Social Insurance Institution register. The cohorts were well characterized and matched for age and sex. The insertion/ deletion polymorphism of the angiotensin-converting enzyme gene and the methionine-->threonine variant at position 235 of the angiotensinogen gene were determined by the polymerase chain reaction technique. The allele frequencies and genotype distributions of both polymorphisms were similar in hypertensive and control subjects. Systolic and diastolic pressures adjusted for age, body mass index, and alcohol consumption did not differ significantly between the different genotypes of the angiotensin-converting enzyme and angiotensinogen genes. The variation at the angiotensinogen and angiotensin-converting enzyme genes did not have any statistically significant synergistic effect on blood pressure levels. In conclusion, the polymorphisms in the reninangiotensin cascade genes do not confer a significantly increased risk for the development of hypertension in this middle-aged, population-based cohort.