The values of procalcitonin (PCT), neopterin, and C-reactive protein (CRP) alone and in combination to differentiate bacterial from viral etiology in patients with lower respiratory tract infections (LRTIs) were evaluated. Sera obtained on the day of hospitalization for LRTI from 139 patients with confirmed bacterial etiology and 128 patients with viral etiology were examined. A further 146 sera from healthy Chinese subjects with no infection were included as controls. The area under the receiver operating characteristic (ROC) curve (area under curve [AUC]) for distinguishing bacterial from viral infections was 0.838 for CRP and 0.770 for PCT (P < 0.05). The AUC for distinguishing viral from bacterial infections was 0.832 for neopterin (P < 0.05). When the markers were used in combination, AUC of ROC (CRP/neopterin) was 0.857, whereas (CRP x PCT)/neopterin was 0.856. Combination of 2 or all 3 of the biomarkers may improve the discriminatory power in delineating bacterial versus viral etiology in LRTI.