DNA in cell nuclei is organized in large loops, which are formed by the binding of DNA to proteins present in a nuclear structure called matrix or scaffold. There is ample evidence that these interactions have not only a structural role, but also a functional one. Studies of these interactions have so far been carried out mainly in vitro. Their relevance, therefore, for the in vivo situation is not proven. We have analyzed the DNA-protein interactions directly in the intact nucleus by means of cross-linking reactions. Cross-linking by UV irradiation and by cis-diamine dichloro platinum (II) have been performed on nuclei from chicken liver and compared. The platinum complex has been found to be more efficient. The proteins complexed to DNA have been isolated and analyzed, and have been found to be enriched in species present in the nuclear scaffold, independently from its method of preparation.