Phosphorylation of a protein (or proteins) of molecular weight 120,000 in the Aplysia abdominal ganglion, as measured by incorporation of [(32)P] or [(33)P]sodium phosphate in vitro followed by separation of the phosphoproteins on sodium dodecyl sulfate-polyacrylamide gels, was specifically stimulated by incubation in the presence of the putative neurotransmitters octopamine or serotonin. The stimulatory effect of octopamine and serotonin was inhibited by phentolamine and methysergide, respectively, and was mimicked by incubation in the presence of dibutyryl cyclic AMP. Label-chase experiments indicated that the difference between control and octopamine-treated ganglia persists for several hours after removal of the drug from the incubation medium. This result suggests that neurotransmitters may produce relatively long-lasting changes in a phosphoprotein in the ganglion, perhaps in postsynaptic cells.