A secondary structure model for 23S ribosomal RNA has been constructed on the basis of comparative sequence data, including the complete sequences from E. coli. Bacillus stearothermophilis , human and mouse mitochondria and several partial sequences. The model has been tested extensively with single strandspecific chemical and enzymatic probes. Long range base-paired interactions organize the molecule into six major structural domains containing over 100 individual helices in all. Regions containing the sites of interaction with several ribosomal proteins and 5S RNA have been located. Segments of the 23S RNA structure corresponding to eucaryotic 5.8S and 2S RNA have been identified, and base paired interactions in the model suggest how they are attached to 2BS RNA. Functionally important regions, including possible sites of contact with 30S ribosomal subunits, the peptidyl transferase center and locations of intervening sequences in various organisms are discussed. Models for molecular ‘switching’ of RNA molecules based on coaxial stacking of helices are presented, including a scheme for tRNA-23S RNA interaction.