The properties of the giant cerebral serotonin-containing neurons of the opisthobranch mollusc Aplysia californica were studied and were compared to the existing data on the giant serotonin-containing neurons (metacerebral cells) of pulmonate mulluscs. Among the properties examined were: axonal distribution, synaptic input and output, pharmacological responses, biophysical characteristics, and plasticity. With only minor exceptions, the properties of the serotonin-containing neurons of Aplysia and of pulmonate molluscs were remarkably similar, and it was concluded that these identified neurons are true homologues. The establishment of the homology of the metacerebral cells of Aplysia to the metacerebral cells of pulmonate molluscs extends the known distribution of these neurons to a second major subclass (Opisthobranchiata) of molluscs. Since pulmonate and opisthobranch molluscs differ substantially in behavioral and anatomical features, the study of the metacerebral cells of these two groups may promote the understanding of the evolutionary adaptation of the nervous system to different environmental pressures.