The effects of bolus intracarotid (IC) infusions of dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) on activity in single or few-fiber carotid chemoreceptor afferent nerve preparations were studied in pentobarbital anesthetized dogs. In addition, the effects of intravenous (IV) infusions of DA were also assessed. IC injections of DA (10 microgram) and (5-HT) (1 microgram) consistently produced a burst of intense activity followed by a period of inhibition. A similar effect was seen with IC NE (20--40 microgram) injections, but the burst of excitation occurred in only 45% of the injections. Inhibition of activity was seen in 88% of the IC NE injections. Low IC doses of all 3 amines produced inhibition of chemoreceptor afferent activity. High doses of DA IV (approximately 60 microgram/kg/))produced excitation followed by depression, while lower doses (approximately 21 microgram/kg) produced only inhibition. The excitatory effects of all 3 amines were blocked by d-tubocurarine (50--435 microgram/kg IV). Inhibitory effects of all 3 amines were blocked by dihydroergotamine (140--270 microgram/kg). The inhibitory effect produced by DA was specifically blocked by haloperidol (50--400 microgram/kg IV). We conclude that DA, NE and 5-HT can modulate carotid body activity by increasing or decreasing responses to physiologic stimuli.