Background: Polymorphisms within genes of the renin-angiotensin system have been associated with an increased risk of cardiovascular disease. We investigated the association of polymorphisms in the angiotensinogen (AGT) and angiotensin II receptor type I (AGTR1) genes with increased intima-media thickness (IMT) and the presence of plaques in carotid arteries. Methods: Subjects (1111) from the Perth Carotid Ultrasound Disease Assessment Study (CUDAS) were genotyped for three polymorphisms: two in the promoter of the AGT gene, G-6A and A-20C; and one in the AGTR1 gene, A I 166C. Results: Using multivariate generalised linear models, the AGT-6A allele (P <0.001) and the AGT-20C allele (P <0.03) were significantly associated with increased mean carotid IMT in females but not in males when adjusted for conventional risk factors. The AGTR1 Al 166C polymorphism did not show any significant relationship to mean IMT. Results suggest that the I allele of the angiotensin converting enzyme insertion/deletion polymorphism may interact with the AGT-6G allele to increase mean carotid IMT in the population as a whole. None of the polymorphisms investigated were significantly associated with the presence of carotid plaques. Conclusion: This study shows that polymorphisms in the angiotensinogen gene are associated with an increased risk of carotid intimal-medial wall thickening in females. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.