Studies on the composition of newly-synthesized nucleolar and ribosomal RNA of the Novikoff rat hepatoma have demonstrated that a portion of these molecules differs from the corresponding portion of similar RNA molecules of normal liver These studies suggest that the genetic defect in cancer cells may be mirrored in aberrations of nucleolar RNA. Accordingly, the possibility exists that modification on this RNA by uptake of specific oligonucleotides and localization on the genes involved in its synthesis may provide a mechanism of inhibition of growth of tumor cells. To test the possibility that tumor cells can take up intact oligonucleotides or RNA molecules, labeled tRNA was incubated with tumor cells in vitro and significant cell uptake of exoge-neous tRNA occurred. Accordingly, it seems possible that one approach to cancer chemotherapy may be the uptake of normal RNA molecules or specifically defined oligonucleotides.