This chapter discusses the idea that spliceosomal ribonucleic acid (RNA) works in fundamentally the same way in all systems is used to develop a cohesive representation of the rearrangement of the most conserved RNA–RNA interactions during splicing. The core of the spliceosome contains a highly conserved RNA structure, suggesting that the chemical events of splicing are based heavily on RNA–RNA interactions. Yet, spliceosomes from different organisms are not exactly the same. Most studies on splicing have used human (HeLa) cells or the yeast, Saccharomyces cerevisiae. Differences in splicing, and the intrinsic strengths and weaknesses of the experimental materials, have restricted some findings to one or other system, but the conservation of small nuclear RNA (snRNA), splicing factor structure, and hnction means that the yeast and human spliceosomes are very similar. Some RNA–RNA interactions are essential in both systems. Some make more important contributions to the function in one system than in the other, at least as assayed in the laboratory. Other interactions have not yet been shown to contribute to the function, but are inferred to be critical for success in the ultimate bioassay evolution. © 1995 Academic Press Inc.