While increasing age is a known risk factor for neuroinvasive West Nile virus (WNV) disease, little is known about risk factors for West Nile fever (WNF). In 2003, United States blood centers identified WN (West Nile) viremic donors using nucleic acid-amplification tests (NATs), making it possible to prospectively determine risk factors for WNF. We report the characteristics of WN viremia among donors at Colorado's largest blood center and risk factors for WNF in viremic donors.Prospective public health surveillance was conducted in WN viremic donors. NAT-reactive donors who developed WNV-specific IgM antibody were considered viremic donors. Demographic data were abstracted from blood center records for all viremic donors aged>or=18 years. Standardized telephone questionnaires were administered a median of 39 days following donation. Donors reporting fever and headache within seven days following donation were considered West Nile fever (WNF) cases.Of 66,771 donations screened from July 1-October 31, 146 (0.22%) were from viremic donors (1:457 donations). Of 135 surveyed donors, 81 (60%) were male. The median age was 49 years (range: 18-78). Forty-one (30%) donors developed WNF; of these, 12 (29%) visited a physician. Other reported symptoms included body aches (98%), eye pain (63%), and skin rash (61%). The risk of WNF was inversely correlated with age (odds ratio: 0.95 for every 1-year increase in age; 95% CI 0.91, 0.99; p=0.008).WN viremia was frequently identified in Colorado blood donors during the 2003 WNV epidemic. The high frequency of WNF and subsequent physician visits among healthy blood donors suggest substantial morbidity from WNF in the general population. The inverse correlation between age and WNF is a new finding and its pathophysiology is unknown.