The solid phase synthesis of sequence specific DNA binding polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids is described. Two monomer building blocks, Boc-Py-OBt ester and Boc-Im acid, are prepared on a 50 g scale without column chromatography. Using commercially available Boc-beta-alanine-Pam resin, cycling protocols were optimized to afford high stepwise coupling yields (>99%). Deprotection by aminolysis affords up to 100 mg quantities of polyamide. Solid phase methodology increases both the number and complexity of minor groove binding polyamides which can be synthesized and analyzed with regard to DNA binding affinity and sequence specificity. The solid phase synthesis of a representative eight-residue polyamide is reported.