The crystal structure of the RNA-binding domain of the small nuclear ribonucleoprotein U1A bound to a 21-nucleotide RNA hairpin has been determined at 1.92 A resolution. The ten-nucleotide RNA loop binds to the surface of the beta-sheet as an open structure, and the AUUGCAC sequence of the loop interacts extensively with the conserved RNP1 and RNP2 motifs and the C-terminal extension of the RNP domain. These interactions include stacking of RNA bases with aromatic side chains of proteins and many direct and water-mediated hydrogen bonds. The structure reveals the stereochemical basis for sequence-specific RNA recognition by the RNP domain.