The solid-phase synthesis of 16alpha-derivatives of 5alpha-androstane-3alpha, 17beta-diol with one, two or three levels of molecular diversity was accomplished using the diethylsilyloxy linker. Libraries with one level of diversity (10 members) and two levels of diversity (40 members) were synthesized in a parallel fashion in good yields and acceptable HPLC purities for the majority of library members. Compounds with three levels of diversity (15 pools) were realized in a split and pool fashion to allow further deconvolution by the positional scanning method. The screening of the generated model libraries revealed interesting preliminary structure-activity relationships related to their antiproliferative activities on androgen-sensitive Shionogi cells. In the case of the two-level library, the presence of a hydrophobic amino acid at R1 (isoleucine (Ile) or phenylalanine (Phe)) and a six-membered ring (aromatic or not) at R2 seems an important requirement for activity. In the three-level library, the amino acid residues isoleucine and phenylalanine clearly provided a better antiproliferative activity than glycine (Gly) and proline (Pro). These model libraries will serve as basis for the generation of larger libraries of peptidosteroids toward the development of therapeutic agents.