This was an association study of genetic polymorphisms to compare the distribution of the genotypes and alleles of the HpaII polymorphism of the atrial natriuretic peptide (ANP) gene in hypertensive patients and normotensive controls. The setting was an outpatient clinic run by a University Department handling referrals from primary care. The patient cohort was composed of 217 subjects, consisting of 109 healthy controls and 108 patients with newly diagnosed or documented hypertension. The genomic DNA was extracted from peripheral blood leukocytes, amplified by polymerase chain reaction, and digested with the restriction enzyme HpaII. H1 and H2 alleles were identified after electrophoresis. The main outcome measures were to identify the frequencies of ANP genotypes and alleles in hypertensive patients and normotensive controls. The H1H1, H1H2, and H2H2 genotypes occurred in 1%, 19%, and 80% of controls and 3%, 18%, and 80% of hypertensive patients, respectively. The frequencies of the H1 and H2 alleles were 0.11 and 0.89 in controls and 0.12 and 0.88 in hypertensive patients. The frequencies of the ANP genotypes and alleles did not differ significantly between controls and hypertensive patients. Our findings differed from previous reports and suggested that this polymorphism is not associated with hypertension in this population.