The ubiquitous white blood cell count (WBC) has rarely been analyzed as a predictor of future mortality. We examined WBC measured in prospective examinations of 2011 initially healthy men in the Normative Aging Study (mean age 47.5), followed for an average of 13.6 years with 27,402 man-years of observation. Between 1970 and 1987, 183 participants died. Mortality rates for men with baseline WBC over 9000 were 12.2/1000 man-years, 1.8-2.5 times those of men with lower WBC in each of three age groups. Proportional hazards models controlling for established risk factors including age, systolic blood pressure, cholesterol and smoking status, found WBC at the baseline exam to be an independent predictor of mortality over the following years. Even within the normal range, a difference of 1000 in the initial WBC increased the risk ratio by 1.2 (95% CI 1.1, 1.3). The relation of initial WBC to mortality was not affected by baseline age, body mass index (BMI), smoking or blood pressure. These findings are not explained by medication effects. We conclude that the WBC is an independent predictor of all-cause mortality.