The nucleotide sequences of cDNAs coding for human salivary proline-rich proteins (PRPs) were determined. Clones cP1 and cP2 contain repetitive regions in which sites for the restriction enzyme HaeIII occur repeatedly; they code for the precursors of acidic PRPs. Clones cP3 to cP7 contain repetitive regions in which BstNI sites occur repeatedly; they code for precursors of basic and glycosylated PRPs. The clones cP3, cP4, and cP5 are identical except that cP4 and cP5 are missing 399 and 459 base pairs, respectively, from the repetitive region of cP3. The sequences at these deletion end points are homologous to the consensus sequences of RNA splicing donor and acceptor sites. This strongly suggests that all three cDNAs are derived from the transcript of a single gene via differential RNA splicing. All of the precursor proteins share a feature--the N-terminal region, following the signal peptide, is acidic, while the remainder of the molecule, made of proline-rich repeats of about 21 amino acids, is basic. Each precursor can generate multiple PRPs by various post-translational cleavages on the carboxylic side of specific arginine residues. The data show how differential RNA splicing and post-translational cleavages could generate a large number of proteins, such as those found in saliva, from a much smaller number of genes.