The recently released drug buspirone is an anxiolytic agent that appears not to have the sedating effects of barbiturates and benzodiazepines, both known to have respiratory depressant effects. Because of its increasing clinical use, we desired to study the effects of buspirone on respiratory control. We therefore determined central neural respiratory responses, measured from phrenic nerve activity, after intravenous administration in paralyzed, vagotomized, and glomectomized cats whose end-tidal PCO2 and body temperature were kept constant. The responses were compared to the effects of the sedating tranquilizer diazepam. Buspirone had a dose-dependent stimulatory effect on respiratory output primarily through an increase of tidal activity but with an increase of frequency in some animals. Associated with this was a shift of the apneic threshold to a lower level of PCO2 without a change of slope or shape of the CO2 response curve. In contrast, diazepam led to a depression of respiration and a shift of the apneic threshold to a higher PCO2. The findings indicate that buspirone does not have the typical neural respiratory depressant actions of diazepam but instead stimulates respiration. Although the findings will need to be shown to apply to human beings, they suggest that buspirone may be a useful drug to treat anxiety in patients without causing undesirable respiratory depression.