Neutrophil peptides, also called defensins, are antimicrobial molecules localized in the azurophil granules of neutrophils. We used a sensitive radioimmunoassay to measure the concentrations of human neutrophil peptides (HNPs) 1-3 in the plasma and blood of 86 healthy volunteers who served as controls and 54 patients with various infections. The respective mean plasma concentrations of HNPs 1-3 in the patients at the onset of bacterial infection, nonbacterial infection, and pulmonary tuberculosis were 4.2, 3.2, and 1.8 times the mean value (+/- SE) for the controls (254.8 +/- 7.1 pg/microL). Plasma concentrations of HNPs 1-3 for the patients were correlated with the peripheral blood neutrophil counts (correlation coefficient = 0.629; P = .0001). The mean concentration (+/- SE) of blood HNPs 1-3 in patients with bacterial infections was higher than the mean value (+/- SE) for controls (10.4 +/- 0.6 ng/microL), whereas the mean concentration (+/- SE) in patients with nonbacterial infections or tuberculosis did not differ from that for controls. Reverse-phase high performance liquid chromatography of plasma samples from patients with bacterial infections showed high concentrations of two precursors of HNPs 1-3, indicating that the biosynthesis of HNPs in neutrophil precursor cells is stimulated in response to infection and/or that the release of pro-HNPs is enhanced. HNPs 1-3 concentrations in the pleural fluid, bronchoalveolar lavage fluid, urine, and cerebrospinal fluid were also elevated in patients with infections. Our results suggest that HNPs have physiological significance in infection and that this family of peptides may be useful in assessing neutrophil function during infection.