A cDNA containing the entire coding region for human nucleolin has been isolated from a lambda gt10 human retinal library using a bovine cDNA probe. The cDNA hybridized to a transcript of 3000 bases from fast-dividing cells, as well as terminally differentiated tissues of several species. Translation of the nucleotide sequence revealed a long open reading frame which predicts a 707 amino acid protein with several distinct domains. These include repeating elements, four conserved RNA-binding regions, a glycine-rich carboxy-terminal domain and sites for phosphorylation, glycosylation and dibasic cleavage. Human and bovine nucleolin exhibited more additions and/or substitutions of aspartate, glutamate and serine residues in the chromatin-binding domains by comparison with the hamster and mouse nucleolins. These differences may be related to species-specific functions in transcription.