The neuropil surrounding sympathetic preganglionic neurons (SPNs) receives an abundant catecholaminergic innervation originating from the brain stem. The effect of catecholamines (CA) released at this spinal level on the activity of SPNs is still controversial as is the extent to which this particular CA transmission is affected by central antihypertensive drugs, such as clonidine and alpha-methyldopa. The present study was initiated, therefore, to determine the effects of iontophoretic applications of CAs and clonidine on the discharges of identified SPNs and to determine the type of receptor mediating the action of these compounds. Extracellular recordings were made with five- or six-barrel electrodes in 20 pigeons anesthetized with urethane, artificially ventilated, and immobilized. Data were obtained on 83 SPNs localized in the three first thoracic segments and identified on the basis of constancy of antidromic activation latency and collision. All of the cells sampled were inhibited by the application of low iontophoretic currents of clonidine and by a series of CAs, including alpha-methylnorepinephrine, epinephrine, and phenylephrine. For each compound, the amount of charge necessary to decrease the level of cell firing to 50% of control was calculated. Using this value as an index of drug potency, the following rank order could be determined: clonidine greater than alpha-methylnorepinephrine greater than epinephrine greater than norepinephrine greater than phenylephrine. The inhibitory effects of both clonidine and norepinephrine were antagonized by iontophoretic applications of the alpha antagonists, yohimbine, piperoxan, and phentolamine. In contrast, the beta antagonist, sotalol, and the alpha 1 antagonist, prazosin, were found ineffective when similarly applied. It is concluded that CAs and clonidine are inhibitory to the maintained activity of SPNs and that an alpha2-adrenergic receptor may be involved in the action of these compounds.