Objective To investigate the association of white blood cell (WBC) count with risk of hypertension. Design Cross-sectional and longitudinal studies. Setting A work site in Japan. Participants A total of 3776 Japanese male office workers aged 23-49 years were enrolled in this study; 2900 hypertension-free [systolic blood pressure (SBP) < 140 mmHg, diastolic blood pressure (DBP) < 90 mmHg, no medication for hypertension, and no past history of hypertension] men were followed up over a 4-year period. Main outcome measures Blood pressure levels and the incidence of hypertension (SBP greater than or equal to 140 mmHg and/or DBP greater than or equal to 90 mmHg or medication for hypertension) according to WBC count at study entry. Results After controlling for potential predictors of hypertension, SBP and DBP levels increased in a dose-dependent manner among both never-smokers and ex-smokers as WBC count increased. Among current smokers, only SBP level increased progressively with WBC count level. The multivariate-adjusted relative risk for development of hypertension compared with the first WBC count quintile was 1.29, 1.21, 1.67, and 1.92 among never-smokers (P for trend = 0.002): and 1.34, 1.46, 1.84, and 1.97 among ex-smokers (P for trend = 0.030) with the second, third, fourth, and fifth quintiles, respectively. Among current smokers, the respective multivariate-adjusted relative risks for hypertension relative to the first WBC count quintile were 0.91, 0.97, 1.08, and 0.84 (P for trend = 0.999). Conclusions WBC count is an important risk factor for hypertension, and the increased risk for hypertension associated with WBC count is more pronounced in nonsmokers. J Hypertens 20:851-857 (C) 2002 Lippincott Williams Wilkins.