To investigate the relationship between 12 candidate genes responsible for water regulation, sodium metabolism and membrane ion transport and essential hypertension (EH) in the Chinese. Linkage analysis of EH was performed in 95 Chinese nuclear families including 477 subjects using a technique of fluorescence-based gene scanning with 12 microsatellite markers. Markers were selected on the chromosomal regions covering 12 candidate genes responsible for regulating water and sodium metabolism and membrane ion transport. These candidate genes included sodium hydrogen exchanger 3, sodium hydrogen exchanger 5, chloride bicarbonate exchanger 3, sodium calcium exchanger 1, mineralocorticoid receptor, plasma membrane calcium ATPase 2, ATPase,Na/K transporting alpha, a-adducin, SA gene, kidney epithelial sodium channel-gamma, vasopressin receptor 1A, and 11beta-hydroxysteroid dehydrogenase type 2 genes. Two-point non-parametric linkage analysis (NPL), maximum LOD score analysis and transmission/disequilibrium test (TDT) were performed using the GENEHUNTER software package. The NPL analysis and LOD score suggested a significant linkage at D12S398 (Z = 2.08, p<0.05 and LOD score = 1.26, p<0.01, respectively). TDT indicated a significant disequilibrium of transmission at the locus chi2 = 9.00, p < 0.005). No significant linkages were found at the other loci tested (p > 0.05 or LOD < -1). In conclusion, D12S398, a marker near the vasopressin receptor 1A gene (V1AR), showed a positive linkage with EH based on the results of three statistical methods (NPL, LOD score, and TDT). This region warrants further exploration.