A variety of experimental data on synthetase-tRNA interactions are examined. Although these data previously had no direct explanation when viewed only in terms of the tRNA cloverleaf diagram, they can be rationalized according to a simple proposal that takes account of the three dimensional structure of tRNA. It is proposed that a major part of the binding site for most or all synthetases is along and around the diagonal side of the tRNA structure, which contains the acceptor stem, dihydrouridine stem, and anticodon. This side of the tRNA molecule contains structural features likely to be common for all tRNAs. Depending on the system, an enzyme may span a small part or all of the region of this side of the molecule. Interactions with other parts of the structure may also occur in a manner that varies from complex to complex. These interactions may be determined, in part, by the angle at which the diagonal side of the flat tRNA molecule is inserted onto the surface of the synthetase.