Epidemiological studies have suggested a link between exposure to persistent organic pollutants (POPs) and hypertension. Cross-sectional associations of serum POP concentrations with the prevalence of newly diagnosed hypertension were investigated in 524 adult participants aged >/=40 years in the National Health and Nutrition Examination Survey 1999-2002. Twenty-one POPs (three polychlorinated dibenzo-p-dioxins (PCDDs), three polychlorinated dibenzofurans (PCDFs), five dioxin-like polychlorinated biphenyls (PCBs), six dioxin-unlike PCBs and four organochlorine (OC) pesticides) were selected because they were detectable in > or =60% of participants. Serum concentrations of PCDDs and PCDFs were associated with prevalent but newly diagnosed hypertension among women, but not among men. Across quartiles of the sum of category numbers of the three PCDDs and the three PCDFs, adjusted odds ratios in women were 1.0, 4.2 (95% confidence interval (CI): 1.0-17.1), 4.5 (1.0-19.9) and 5.0 (1.2-21.5) (P for trend=0.08) and 1.0, 2.6 (0.8-9.0), 5.9 (1.7-20.0) and 4.2 (1.3-14.3) (P for trend=0.01), respectively. On the other hand, PCBs tended toward positive association with hypertension only among men. Adjusted odds ratios in men in the highest quartiles of the sum of category numbers of the dioxin-like and non-dioxin-like PCBs were 2.3 (0.8-6.6) and 2.8 (0.9-8.5) (P for trend=0.11 or 0.04), respectively. OC pesticides were not clearly associated with hypertension in either gender. Hypertension had gender-specific associations with serum concentrations of some POPs. Considering the common presence of exposure to POPs in the general population, these findings need to be clarified in prospective studies.