In 26 infants and children with septicemia or bacterial meningitis, significantly elevated plasma levels of elastase-alpha 1-proteinase inhibitor (E-alpha 1-PI) were present at time of recognition of infection, even in those patients with neutropenia (range of reference values: 25 to 190 micrograms/L, n = 142; patients: 444 to 2049 micrograms/L, n = 26). After initiation of therapy, normalization of E-alpha 1-PI levels was observed in all patients who recovered from infection. In addition, 18 of 19 children with bacterial meningitis had increased cerebrospinal fluid concentrations of E-alpha 1-PI above the range of normal (range of reference values: 0 to 39 micrograms/L, n = 62; patients: 30 to 3490 micrograms/L, n = 19); concentrations of E-alpha 1-PI in bacterial meningitis were significantly increased when compared with those in aseptic meningitis (range 25 to 194 micrograms/L; n = 15). In 30 patients with local bacterial infections (pneumonia, urinary tract infections, etc.), E-alpha 1-PI was also elevated. These data suggest that E-alpha 1-PI is a sensitive indicator of systemic and local bacterial infection in childhood.