Improvements to the Fmoc solid-phase synthesis of N-methylpyrrole (Py) and N-methylimidazole (Im) polyamides were examined. It was found that a different combination of coupling agents and activators, and the introduction of a dimer unit significantly enhanced the yield of polyamides. Using this improved method, various types of polyamides were synthesized. The uptake and localization of polyamides in living mammalian cells were investigated using FITC labeled Py-Im polyamides.