We evaluated efficacy and safety of naltrexone for antagonizing carfentanil immobilization in 12 captive Rocky Mountain elk (Cervus elaphus nelsoni) using a randomized incomplete block experiment. In three replicate trials, elk were hand-injected with 10 μg carfentanil citrate/kg body weight intramuscularly. Fifteen min after each elk became recumbent, we administered naltrexone HCl (25% of dose intravenously, 75% subcutaneously) dosed at 0 (control), 25, 50, or 100 mg/mg carfentanil; after an additional 15 min of immobilization, controls received 5(H) mg naltrexone HCl/mg carfentanil. Elk were immobilized in 34 of 36 attempts; the mean (±SE) induction time was 3.1 ± 0.2 min. Regardless of dose, all elk stood <9 min after receiving naltrexone; controls remained immobilized until they received antagonist. Mean recovery times did not differ with increasing naltrexone dose (P = 0.31) or among individuals (P = 0.16). None of the elk receiving 100 or 500 mg naltrexone/mg carfentanil renarcotized, but three of eight and seven of nine elk receiving 50 and 25 mg naltrexone/mg carfentanil, respectively, showed signs of mild renarcotization 8 to 24 hr later (P = 0.0002). We observed no adverse clinical effects in elk receiving ≤500 mg naltrexone/mg carfentanil. Based on these data, we recommend 100 mg/mg carfentanil as a minimum effective dose for rapidly antagonizing immobilization and preventing renarcotization.