Microneedle patches contain micrometer-scale needles coated with bioactive agents for minimally invasive drug delivery to the skin. In this study, we introduce layer-by-layer approaches to the fabrication of ultrathin DNA- and protein-containing polyelectrolyte films (or "polyelectrolyte multilayers", PEMs) on the surfaces of stainless steel microneedles. DNA-containing PEMs were fabricated on microneedles by the alternating deposition of plasmid DNA and a hydrolytically degradable poly(beta-amino ester). Protein-containing PEMs were fabricated using sodium poly(styrene sulfonate) (SPS) and bovine pancreatic ribonuclease A (RNase A) conjugated to a synthetic protein transduction domain. Layer-by-layer assembly resulted in ultrathin. uniform, and defect-free coatings on the surfaces of the microneedles, as characterized by fluorescence microscopy. These films eroded and thereby released DNA or protein when incubated in saline or when inserted into porcine cadaver skin and deposited DNA or protein along the edges of microneedle tracks to depths of similar to 500 to 600 mu m. We conclude that PEN-coated microneedles offer a novel and useful approach to the transdermal delivery of DNA- and protein-based therapeutics and could also prove useful in other applications.