Vertebrate ribosomal protein mRNAs share structural features in the 5' untranslated region implicated in the control of their translation. A pyrimidine tract, at the 5' end, is considered the common cis-acting element, but the control requires also the integrity of the conserved downstream region. These sequences interact in vitro with proteins, which may represent the trans-acting factors for a common regulation. The protein that binds the pyrimidine tract has been identified as La and its binding in vitro depends on interaction with a protein factor. In the present study, by purification, microsequencing and immunoprecipitation analysis we have identified the protein that interacts with the region downstream of the pyrimidine tract as the Xenopus laevis cellular nucleic acid binding protein (CNBP). The interaction of this protein with the conserved region of various ribosomal protein (rp)-mRNAs suggests a class-specific recognition. The binding of CNBP to the target region requires the assistance of a protease-sensitive factor, that dissociates after complex formation. Some evidence suggests that this may be the same factor that assists the binding of La to the 5' untranslated region (UTR) of the rp-mRNAs. Considering that CNBP and La come in contact with two typical regions of the 5' UTR, essential for regulation, their interaction with the assisting factor may exert a modulating activity on the translational control of ribosomal protein mRNAs.