Secreted proteins and membrane proteins play key roles in the formation, differentiation, and maintenance of multicellular organisms. In this study, we undertook to characterize these protein types in the central nervous system of the marine snail Aplysia kurodai using a yeast-based signal sequence trap method. One hundred and three cDNA clones were obtained by screening 300,000 clones from the signal sequence trap cDNA library. Of these, twelve were identical to previously identified Aplysia genes, 19 were related to known proteins in other organisms, and 54 clones were novel. These 54 new genes had high signal peptide scores or were found likely to contain a transmembrane domain sequence. Only 18 of the 103 clones proved to be false positive. The study demonstrates that the signal sequence trap method is an effective tool for Isolating Aplysia genes encoding secreted and membrane proteins.