We have found that the growth of normal human keratinocytes, grown in serum-free medium, was significantly stimulated by the antisense oligonucleotide of retinoblastoma susceptibility gene (Rb). Normal human keratinocytes were exposed to phosphorothionate oligonucleotides which were complementary to translation initiation codon of Rb gene. The growth of keratinocytes was enhanced by the antisense, but not the sense, oligonucleotide of Rb gene in a dose-dependent manner from 1 to 10 microM. The Rb antisense oligonucleotide, however, did not result in any appreciable change in transcription of the gene when examined by reverse-transcription polymerase chain reaction (RT-PCR) analysis or in the protein expression and the phosphorylation pattern when examined by immunoprecipitation and Western blotting.