Pre-mRNA splicing in eukaryotes requires joining together the nucleotides of the various mRNA-coding regions (exons) after recognizing them from the normally vastly superior number of non-mRNA-coding sequences (introns). For three excellent reviews on general splicing and its regulation, refer to references 14, 62, and 70. In eukaryotes, the vast majority of splicing processes are catalyzed by the spliceosome, a very complex RNA-protein aggregate which has been estimated to contain several hundred different proteins in addition to five spliceosomal snRNAs (1, 54, 62, 63, 81, 109). These factors are responsible for the accurate positioning of the spliceosome on the 5! and 3! splice site sequences. The reason why so many factors are needed reffects the observation that exon recognition can be affected by many pre-mRNA features such as exon length (5, 97), the presence of enhancer and silencer elements (8, 62), the strength of splicing signals (45), the promoter architecture (29, 55), and the rate of RNA processivity (86). In addition, the general cellular environment also exerts an effect, as recent observations suggest the existence of extensive coupling between splicing and many other gene expression steps (69) and even its modification by external stimuli (96). In the midst of all this complexity, it has also been proposed that pre-mRNA secondary structures can potentially inffuence splicing activity. However, despite a steady increase of reports invoking their effects on splicing regulation, the last specific review on this subject is now more than 10 years old (3). Here, we propose to address again this specific issue in the current perspective of the general field. Before we do this, however, we have to answer a basic question.