Objective A common threonine481serine polymorphism (T481S) has been shown in vitro to strongly activate the chloride channel Kb (CLC-Kb) expressed in the kidney, and the 481S allele has been associated with human hypertension. The study aim was to evaluate the association of the T481 S polymorphism with blood pressure (BP) levels and the BP progression rate in Swedes. Design and methods The cardiovascular cohort of the Malmo Diet and Cancer (MDC) study is a population surveyed in 1991-1996 (n = 6103, DNA available on n = 6055), 53% of whom had also been examined 11 +/- 4.4 years earlier in the Malmo preventive Project (MPP) Hypertension was defined as having BP above 140/90 mmHg or being on antihypertensive therapy (AHT). Carriers of one or two copies of the 481S allele were compared with T481T homozygotes (noncarriers). Results Among individuals without AHT in the MIX study (n = 4988) there was no difference between carriers (n = 1164, 23%) and noricarriers (n = 3824, 77%) in systolic BP (139.3 +/- 8.3 vs 139.2 +/- 8.3 mmHg, P=0.82) or diastolic BP (86.0 +/- 9.1 vs 86.0 +/- 9.2 mmHg, P = 0.95). In subjects free from AHT at the Ill and Ill studies (n = 2627) there was no difference between carriers (n = 607, 23%) and noricarriers (n = 2020, 77%) in progression of systolic BP (2.1 +/- 2.6 vs 2.0 +/- 2.8 mmHg/year, P = 0.72) or diastolic BP (0.57 +/- 1.4 vs 0.58 +/- 1.6 mmHg/year, P = 0.85) from Ill to Ill Multivariate analysis gave no support of interaction between the CLC-Kb 481S polymorphism, gender, age or body mass index regarding their effect on BP. Conclusion Our data do not support a role of the CLC-Kb T481S polymorphism in BP regulation in Swedes.