This study examined the direct effects of MS-222 (tricaine methanesulfonate), a sodium-channel blocking local anesthetic, on respiratory motor output using an in vitro brainstem preparation of adult North American bullfrogs (Rana catesbeiana). Bullfrogs were anesthetized with halothane, the brainstem removed and superfused with artificial cerebrospinal fluid (aCSF) containing MS-222 at concentrations ranging from 0.1 µM to 1000 µM. At the lowest concentration of MS-222, respiratory frequency (f_R) increased significantly (P<0.05), but at higher concentrations, f_R progressively decreased and was abolished in all preparations at 1000 µM (P<0.01). Respiratory burst amplitude and burst duration was not affected by MS-222. The frequency of 'non-respiratory' neural activity did not significantly change with the addition of MS-222 below 1000 µM. These data indicate that MS-222 has a significant, direct effect on respiratory motor output from the central nervous system, producing both excitation and inhibition of fictive breathing. The results are consistent with other studies demonstrating that low concentrations of anesthetics generally cause excitation followed by depression at higher concentrations. Although the mechanisms underlying the excitatory effects of MS-222 in this study are unclear, they may include increased excitatory neurotransmission and/or disinhibition of inputs to the respiratory central pattern generator.