To determine whether a trans-synaptic mechanism triggered the effects of reserpine on adrenomedullary mRNAs encoding the norepinephrine transporter and tyrosine hydroxylase, we administered 10 mg/kg reserpine to rats after unilateral splanchnicotomy, and examined their adrenal medullas using quantitative in situ hybridization. Splanchnicotomy did not alter the decrease in norepinephrine transporter mRNA that follows reserpine administration, but diminished the reserpine-induced increase in tyrosine hydroxylase mRNA by almost 80%. Despite the latter effect, reserpine still induced a significant increase in tyrosine hydroxylase mRNA in denervated adrenal medullas, compared to vehicle-treated adrenal medullas. These results show that a trans-synaptic mechanism does not trigger the decrease in adrenomedullary norepinephrine transporter mRNA following reserpine. In addition, an innervation-independent mechanism mediates a portion of the reserpine-induced increase in adrenomedullary tyrosine hydroxylase mRNA.