Complexes composed of RNA and protein play essential roles at multiple levels in the gene expression pathway, including transcription, RNA processing, transport, and translation. In this chapter, we describe a generally applicable system that allows the function of specific RNA-protein complexes to be investigated. Previous strategies used to study the function of small nuclear ribonucleoprotein particles (snRNPs) in vitro have included inhibition with specific antibodies (1, 2), RNase H cleavage of targeted snRNAs in the presence of complementary DNA oligonucleotides (24), and “antisense masking” of specific snRNA sequences with 2′-OMe RNA oligonucleotides (7–9). A potential disadvantage of these methods is that an RNP particle inactivated, but not physically removed from an extract may still retain separate functional domains.