There is considerable epidemiological and clinical evidence that regular garlic supplementation reduces cardiovascular risk. In this study, we have investigated the hypothesis that dietary garlic supplementation increases tissue blood flow and this is mediated by the vasodilatory actions of interleukin-6 (IL-6). Venous occlusion plethysmography was used to measure resting calf blood flow before and after oral administration of 600 mg of garlic tablets once daily for 7 days in 13 young healthy female volunteers (treatment group) and 13 female controls matched for age and body mass index (BMI). Blood samples were obtained at the time of plethysmography to measure plasma levels of IL-6, nitrate, nitrite and c-GMP. In the treatment group, calf blood flow increased significantly from 3.01 (2.56 to 3.3) ml min(-1) 100 mL(-1) of tissue before garlic to 3.46 (3.0 to 4.03) ml min(-1) 100 mL(-1) of tissue after 7 days of garlic (P = 0.001). Plasma IL-6 concentrations increased significantly from 54.6 (32.3 to 151.6) mcg/mL before to 151 (135.75 to 422.3) mcg/mL after 7 days of garlic (P = 0.02). However, there was no significant change in the plasma levels of nitrate, nitrite and c-GMP after the garlic (P = 0.4, 0.9 and 0.65 respectively). In the control group, resting calf blood flow and plasma levels of IL-6, nitrite, nitrate and c-GMP remained unchanged after 7 days (P = 0.62, 0.92, 0.28 and 0.35 respectively). Calf blood flow showed a non-linear correlation with plasma IL-6 levels after garlic supplementation (r = 0.86, p = <0.001) but not before. There was no significant relationship between blood flow and plasma nitrate, nitrite and c-GMP in either groups and between blood flow and IL-6 in the control group. These data suggest that garlic supplementation increases resting tissue blood flow and this may be mediated by IL-6.