Synthetic combinatorial libraries (SCLs) consisting of millions of compounds are proving to be a powerful source for the identification of novel biologically active compounds (see ref. 1–3). Individual compounds having potent biological activities can now be rapidly identified from pools containing millions of other compounds (4–9). As first presented by this laboratory, nonsupport-bound SCLs have been shown to be usable in virtually any assay system. In an expansion of SCL concepts and diversities, the original peptide SCLs have recently been transformed using a “libraries from libraries” approach (7,10,11a) to yield peptidomimetic and organic libraries having entirely different physical, chemical, and biological properties relative to the peptide SCLs used as starting materials. The screening of a SCL composed of 50 million peptidomimetics (7) has yielded individual active compounds that had no homology to those found in the starting SCLs. We describe here improved methods (10) developed for the transformation of such libraries.