The topical application of isoflurane and sevoflurane compounded jellies has been used successfully to anesthetize anurans. Although sevoflurane is a less tissue-soluble anesthetic than isoflurane, it is unknown whether tissue solubility affects anesthesia after topical application. The purpose of this study was to determine time to loss and return of righting reflex in eight American green tree frogs, Hyla cinerea, after topical application of compounded isoflurane or sevoflurane jelly. Frogs were placed into a container with either 2 ml of isoflurane or sevoflurane jelly. Containers were intermittently inverted until loss of righting reflex was observed. Frogs were then removed, rinsed clean of the jelly, and placed in new containers in dorsal recumbency. Frogs were observed until their righting reflex returned. Four frogs initially tested with isoflurane developed skin lesions, and two subsequently died. Accordingly, the isoflurane jelly was discontinued. Frogs exposed to isoflurane lost their righting reflex 90 ± 20 sec after exposure and frogs exposed to sevoflurane jelly lost their righting reflex 112 ± 33 sec after exposure to the anesthetic. Frogs exposed to isoflurane had their righting reflex return 2,659 ± 733 sec after having the jelly removed, and frogs exposed to sevoflurane had their righting reflex return 1,085 ± 1,204 sec after having the jelly removed. There was no significant difference between loss of righting reflex times (P = 0.30) between anesthetics; however, there was a significant difference in the time to the return of the righting reflex (P = 0.04), with isoflurane recovery being 4.5 times longer than sevoflurane. None of the frogs receiving sevoflurane jelly developed skin lesions. Based on this study, topically applied sevofluane jelly may be a useful anesthetic for American tree frogs, whereas isoflurane jelly, at the dose used, should be avoided.