To the Editor: The magnitude of sevoflurane’s (and enflurane’s) effect on fluoride inhibition of pseudocholinesterase (PCHE) deserves attention in modern anesthetic practice. Nearly all studies dealing with this topic1–3 refer to the study of Kambam et al.4 who reported an inhibition of PCHE between 16 to 73% with 10 to 100 μmol·L–1 fluoride, the concentrations usually obtained during sevoflurane (and enflurane) anesthesia. Since we could not confirm this inhibition with mivacurium and butyrylthiocholine as substrates and at temperatures between 28 to 37°C3,5 we investigated fluoride inhibition of PCHE with benzoylcholine at 25°C, the substrate and temperature Kambam et al. used in their study, and at 37°C, the temperature currently recommended for determination of enzymatic activity. After approval by our Local Ethics Committee and with written informed consent, serum samples of eight healthy volunteers were obtained, spiked with fluoride (0, 10, 50 and 100 μmol·L–1) and adjusted to 25°C and 37°C, respectively. Thereafter, 50 μmol·L–1 benzoylcholine were added, and at timed interval aliquots were withdrawn to measure the concentrations of benzoylcholine by high-performance liquid chromatography. After calculating the half-lives with KINETICA 2000 (InnaPhase Corp. Philadelphia, PA, USA) a one-factor (fluoride concentration) analysis of variance with a post hoc Dunnett test was performed at each temperature, using the fluoride-free sample as the control category. The results are presented in the Figure. At 25°C there was an increase of the benzoylcholine half-time of 9.3% with 10 μmol·L–1 fluoride, and a 36% increase with 50 μmol·L–1 fluoride. The 68% increase in benzoylcholine half-time was significant (P < 0.05) at a concentration of 100 μmol·L–1. In contrast, no change was observed over the same range of fluoride concentrations at 37°C. We thus confirm one aspect of the study of Kambam et al.4 who measured PCHE activity at 25°C with a photometric assay. In contrast, when using a high-performance liquid chromatography assay at clinically relevant body temperature (37°C) and with fluoride concentrations up to 100 μmol·L–1, fluoride inhibition of PCHE is not apparent, whether using the substrates mivacurium and butyrylthiocholine3,5 or benzoylcholine, as reported here. In conclusion, the influence of substrate and temperature on fluoride inhibition of PCHE must be taken into consideration when interpreting the results of investigations with sevoflurane and enflurane.