Among obese individuals, increased sympathetic nervous system (SNS) activity results in increased renin and aldosterone production, as well as renal tubular sodium reabsorption. This study determined the associations between adipokines and selected measures of the renin-angiotensinogen-aldosterone system (RAAS). The sample consisted of 1970 men and women from the Multi-Ethnic Study of Atherosclerosis who were free of clinical cardiovascular disease at baseline and had blood assayed for adiponectin, leptin, plasma renin activity (PRA) and aldosterone. The mean age was 64.7 years and 50% were female. The mean (s.d.) PRA and aldosterone were 1.45 (0.56) ng ml(-1) and 150.1 (130.5) pg ml(-1), respectively. After multivariable adjustment, a 1-s.d. increment of leptin was associated with a 0.55 ng ml(-1) higher PRA and 8.4 pg ml(-1) higher aldosterone (P<0.01 for both). Although adiponectin was not significantly associated with PRA levels, the same increment in this adipokine was associated with lower aldosterone levels (-5.5 pg ml(-1), P=0.01). Notably, the associations between aldosterone and both leptin and adiponectin were not materially changed with additional adjustment for PRA. Exclusion of those taking antihypertensive medications modestly attenuated the associations. The associations between leptin and both PRA and aldosterone were not different by gender but were significantly stronger among non-Hispanic Whites and Chinese Americans than African and Hispanic Americans (P<0.01). The findings suggest that both adiponectin and leptin may be relevant to blood pressure regulation via the RAAS, in that the associations appear to be robust to antihypertension medication use and that the associations are likely different by ethnicity.