The activity of the epithelial sodium channel (ENaC) has been related to salt-sensitivity especially in Liddle Syndrome, a severe form of salt-sensitive hypertension (Furuhashi et al., 2005). The selective ENaC blocker, amiloride, has been shown to be effective in reducing blood pressure not only in Liddle’s syndrome (Botero-Velez et al., 1994) but also in blacks with T594M polymorphism of ENaC (Baker et al., 2002). Every population is heterogenous for salt-sensitivity. It is therefore of interest whether amiloride will block the channel in salt-resistant individuals as well as salt-sensitive persons especially as amiloride has been suggested as a sole anti-hypertensive agent in blacks (Baker et al., 2002). Baseline blood pressure was measured in 22 normotensive (NT) and 42 age-matched hypertensive (HT) subjects earlier divided into salt-sensitive (NT = 11; HT = 22) and salt-resistant (NT = 11; HT = 20) subgroups (Elias et al., 2011). Subjects were salt-loaded with 200mmol Na+/day for 5 days. Blood pressure was thereafter measured to determine the effect of the salt-load. After one week wash-out period, subjects ingested a combination of the salt-load and 5mg amiloride tablets daily for 5 days. The effect of the combination on blood pressure was determined. Ethical clearance for this study was obtained from the College of Medicine, University of Lagos. Data are presented as mean ± S.E.M., compared with ANOVA and appropriate post-hoc tests. Baseline systolic blood pressure (SBP) and daistolic blood pressure (DBP) were similar (p>0.05) in the salt-sensitive (SBP 121.5±2.8 mmHg; DBP 80.9±0.8 mmHg) and salt-resistant (SBP 120.7±2.4 mmHg; DBP 80.2±1.6 mmHg) NT subjects and among the salt-sensitive (SBP 144.7±3.6 mmHg; DBP 92.9±2.4 mmHg) and salt-resistant (142.9±4.8 mmHg; DBP 99.2±2.0 mmHg) HT subjects. Following the salt-load, blood pressure changed significantly (p<0.01) (+7.7±2.6% SBP; +11.6±2.1% DBP) among the salt-sensitive NT subjects but marginally (p>0.05) (+0.6±1.9% SBP; -0.5±2.6% DBP) among the salt-resistant NT subjects. Similarly, there were significant (p <0.001) pressor responses to the salt load among the salt-sensitive (+7.8±1.7% SBP; +11.6±1.7% DBP) but not among the salt-resistant (SBP +2.1±1.7%; DBP -2.2±1.4%) HT subjects. Salt plus amiloride-loading led to significant reduction in SBP among salt-sensitive subjects (p<0.001) (-9.9±2.1% NT; -12.9±2.0% HT) and salt-resistant subjects (p<0.05) (-6.5±2.0% NT; -10.0±1.5% HT) compared with salt-loading alone. Similarly, the combination significantly reduced DBP among salt-sensitive (p<0.001) (-13.9±3.4% NT; -10.4±2.8% HT) subjects but reduced DBP in salt-resistant (-7.1±1.7%, p<0.001) HT subjects only. The effect of ENaC blockade by amiloride are similar among salt-sensitive and salt-resistant subjects. These results suggest that salt-resistance does not preclude treatment of hypertension with amiloride.