We have previously shown that the herpes simplex virus type 1 (HSV-1)-specified glycoprotein C (gC-1) produced in epitheloid cells contains epitopes of peptide nature, which are dependent on galactose of oligosaccharides for their expression. In the present communication we report that these epitopes are expressed in a mouse neuroblastoma cell line (C1300) with low levels of galactosyl transferases. However, in place of galactose the glycoprotein from C1300 cells was found to contain oligosaccharides with additional fucose units. Fucosidase treatment, but not galactosidase treatment, abolished the antigenic activity of the carbohydrate-dependent epitopes. Altogether the results indicated that the carbohydrate-dependent epitopes of gC-1 from C1300 cells were stabilized by peripheral sugars of N-linked oligosaccharides rather than O-linked ones and that fucose could substitute for terminal galactose in promoting the activity of the carbohydrate-dependent epitopes. This is the first demonstration of the involvement of fucose in the establishment of a carbohydrate-dependent epitope of peptide nature. The results also demonstrated that reversible carbohydrate-peptide interactions were responsible for the activity of the carbohydrate-dependent epitopes.