The serine/threonine kinase With-No-Lysine (K) Kinase 1 (WNK1) activates the thiazide-sensitive Na+/Cl− cotransporter through phosphorylation of STE20/SPS1-related proline/alanine-rich kinase, another serine/threonine kinase encoded by STK39. The aim of this study was to look for association between WNK1 and STK39 gene variants, and blood pressure (BP) and hypertension. Seven hundred seventy-nine Caucasian hypertensive patients (HYP) recruited in 6 academic centers from Belgium, and 906 normotensive (NT) controls were genotyped for 5 single nucleotide polymorphisms—rs3754777, rs6749447, rs35929607 (STK39), rs1468326, and rs765250 (WNK1)—using the Snapshot method. The rare TT genotype at the rs3754777 locus (STK39) was overrepresented in HYP versus NT (7.3% vs 3.0%, P = 0.0002). In the whole study population, the multivariable-adjusted odds ratio (OR) for having hypertension associated with the TT genotype was 5.9 (95% confidence interval: 2.2–15.6), and systolic BP was 10 mm Hg higher in TT compared with wild-type subjects (140.1 vs 130.4 mm Hg, P = 0.002). Similarly, the AA genotype at the rs1468326 locus (WNK1) was twice as frequent in HYP versus NT (5.5% vs 2.3%, P