Microinjection of the alpha 2-adrenoceptor agonist, clonidine (CLON; 1.0 microgram/0.1 microliter) effected a virtually complete suppression of the spontaneous activity of noradrenergic neurons of the locus coeruleus in freely moving cats. This effect lasted for approximately 90 min and was reversible by systemic administration of the alpha 2-adrenoceptor antagonist, yohimbine. In contrast, CLON had no consistent effect on the activity of neighboring non-noradrenergic neurons. These results provide additional evidence for the direct inhibition of central noradrenergic neurons by CLON by demonstrating such effects independent of anesthesia or the behavioral effects of systemic drug administration. More generally, these findings demonstrate the usefulness of a technique in which small amounts of drug can be applied in small volumes to produce a neuropharmacologically specific effect upon locally recorded neurons in behaving animals.