These studies examined activity of the diaphragm and a laryngeal dilator, the posterior cricoarytenoid, following 3 levels of intravenous and cerebral ventricular administration of cocaine. Both administration routes induced extremely high respiratory rates with enhanced tonic and phasic electromyographic activity, and affected patterning similarly in upper airway and diaphragmatic muscles. Both intravenous and intraventricular administration induced a rise in core and brain temperature related to the route of administration; however, the tachypnea was only loosely related to the hyperthermia. Intraventricular administration resulted in a more rapid onset of peak respiratory rates, and a faster decline than an intravenous route. Different dose levels elicited similar elevated respiratory rates, but higher intravenous doses also resulted in extensive hypertonicity with intermittent phasic movements. Tachypnea continued between these phasic efforts. The phasic events associated with high doses were accompanied by sustained inspiratory efforts; however, no evidence of obstructive apnea was found. These data suggest that cocaine can modify respiratory patterning by inducing a centrally mediated tachypnea and by eliciting sustained, intermittent inspiratory efforts.