Study Objective. To determine the disposition of cefepime in patients with cystic fibrosis compared with healthy controls.Design. Open‐label, single‐dose study.Setting. Laboratoire de Pharmacocinétique Clinique, Université Laval, Québec, Canada.Patients and Subjects. Twelve patients with the confirmed diagnosis of cystic fibrosis (CF) and 12 healthy volunteers. One subject with CF withdrew for personal reasons; the data of another patient were excluded from the evaluation of renal values due to incomplete urine collection.Interventions. A single 2000‐mg dose of cefepime was administered as a 30‐minute intravenous infusion. Healthy subjects did not use any other drugs throughout the study. Those with CF refrained from taking prophylactic antibiotics prior to and during the study, but continued to use pancreatic enzymes, multivitamins, and β‐agonist and/or steroid inhalers. One patient continued insulin treatment.Measurements and Main Results. Cefepime's maximum concentration was approximately 150 μg/ml at the end of the infusion, half‐life 2‐2.5 hours, and urinary recovery 80% in both groups. No statistically significant difference was seen in any of the pharmacokinetic values between the groups, except for the mean residence time (2.03 ± 0.26 vs 2.39 ± 0.37 hrs; p<0.02). Total clearance was 19% higher in patients with CF than in healthy volunteers (119.7 ± 20.1 vs 103.5 ± 19.8 ml/min), perhaps due to higher renal (95.1 ± 12.4 vs 85.1 ± 12.0 ml/min) and/or nonrenal (25.4 ± 13.1 vs 18.4 ± 12.0 ml/min) clearances in subjects with CF.Conclusions. The disposition of cefepime is not significantly affected by CF, and dosage adjustment appears not to be necessary in these patients.