The effect of enflurane and isoflurane with and without nitrous oxide (N2O) on human polymorphonuclear leukocyte (PMNL) microbicidal function was studied. Bacterial killing was determined using a standard pour-plate technique and by oxidative activity as measured by chemiluminescence (CL). No killing ofEscherichia coli, Klebsiella pneumoniae, or Staphylococcus aureuswas seen at bacteria:PMNL ratios of 1 or 10:1 with either enflurane or isoflurane at concentrations greater than normally used (3%). However, at a clinically relevant concentration of 2%, a significant inhibition of bacterial killing was observed with enflurane but not isoflurane at a bacteria:PMNL ratio of 100:1. The CL response also was decreased significantly (28% inhibition) by 2% enflurane. N2O 70% plus O230% had no effect on bactericidal activity or chemiluminescence alone or in combination with enflurane or isoflurane. The inhibition of bacterial killing and CL following enflurane exposure could be reversed by exposing the enflurane treated PMNL to air for 30 min. These results suggest that enflurane is able to inhibit PMNL microbicidal activity only when the PMNL are stressed with a large bacterial challenge or stimulus. This inhibition is temporal and only occurs during enflurane exposure.