Angiotensin II type 1 receptor (AT1) mediates the vasoconstrictive and growth-promoting effect of angiotensin II in humans. It has been reported that a polymorphism of the AT1 gene (an A/C transversion at position 1166: A-C1166) occurs more frequently in resistant hypertensives taking two or more antihypertensive drugs. On the contrary, a recent study of the influence of the A-C1166 polymorphism on aortic stiffness demonstrated that the distribution of the genotypes did not differ between normotensive and hypertensive subjects. In addition, a recent population-based survey of Caucasian hypertensives reported lower blood pressure values in CC homozygotes than in heterozygotes and AA homozygotes. Because of these controversial results and the lack of a sufficient amount of data the present study was designed to assess the contribution of the AT, gene A-C1166 polymorphism to resistant essential hypertension. Forty-eight subjects with resistant essential hypertension (HT) and 48 normotensive (NT), age and sex-adjusted controls (from a population of 300 healthy blood donors) were selected. All subjects were genotyped for the A-C1166 polymorphism in the 3'-UTR of the AT1 gene using PCR-based techniques. The influence of genotype on blood pressure (BP) was investigated using ANOVA Randomized Complete Block (ANOVA RCB) design according to sex, age and BMI. There were no significant differences in allele or genotype frequencies between HT and NT subjects (X2 = 0.61; P = NS). In HT subjects higher values of systolic blood pressure were associated with the C allele of the AT1 gene only in older and overweight patients (P < 0.001 and P < 0.001, respectively). Also in HT patients an association between the presence of the C allele of the AT1 gene and higher values of diastolic blood pressure was present in overweight patients (P = 0.001). These results suggest that in resistant hypertensive subjects the AT1 A-C1166 polymorphism is potentially involved in the regulation of blood pressure. As the effects of genotypes on blood pressure are pronounced in older and overweight subjects this polymorphism may amplify the effects of age and BMI on resistant essential hypertension.