The effect of halothane on the electrical activity of inspiratory neurons of the nucleus tractus solitarius (NTS) was studied in decerebrate, paralyzed, mechanically ventilated cats. Simultaneous recording of the activity of the neurons of the NTS and the phrenic nerve was done to identify the inspiratory neurons. Cells whose firing activity was synchronous with that of the phrenic nerve were considered inspiratory neurons. Administration of 1% and 1.5% halothane in oxygen induced a dose-dependent depression of the cell activity (spikes/s) with the cervical vagi intact or severed. Five and ten minutes after inhalation of 1% halothane, the cell activity (mean +/- SE) expressed as per cent of the control was 55.3 +/- 9 and 27 +/- 7, respectively (P less than 0.001), before bilateral cervical vagotomy. The corresponding values for 1.5% halothane were 25 +/- 10.1 and 5.6 +/- 3, respectively. Upon termination of halothane administration, the cell activity gradually returned toward the control level. The cell response to halothane was not affected by bilateral cervical vagotomy. Hypercapnia produced by inhalation of 5% CO2 increased the cell activity, but halothane caused profound depression of the cells even in the presence of hypercapnia. Based on these results, it may be concluded that: halothane has inhibitory effects on the activity of the inspiratory neurons of the NTS; and halothane-induced respiratory depression has a central component and that the NTS may serve as a site of action of halothane for its respiratory depressant effect.