1. Phosphoproteins of different regions of the Hirudo medicinalis central nervous system have been analysed by means of two-dimensional electrophoresis. 2. Serotonin, 8-Br-cAMP and phorbol 12,13-dibutyrate stimulate phosphorylation of a number of proteins whose isoelectric points and molecular weights are presented. 3. A group of proteins of 78 kDa and pI = 6-6.5, whose level of phosphorylation increases in the presence of serotonin, 8-Br-cAMP and phorbol ester, is observed only in segmental but not in cephalic or caudal ganglia. 4. The putative roles of these phosphoproteins are discussed.