Porous polyethylene (PP or Medpor) is an alloplastic material used worldwide for craniofacial reconstruction. Although several clinical studies are available, there is a lack as regard the genetic effects. Because PP is always fixed on bone and the mechanism by which PP acts on osteoblasts is unknown, we therefore attempted to address this question by using microarray techniques to identify genes that are differently regulated in osteoblasts exposed to PP. By using DNA microarrays containing 19,200 genes, we identified in osteoblast-like cell lines (i.e. MG-63) cultured on PP several genes where expression was differentially regulated. The differentially expressed genes cover a broad range of functional activities: 1) signal transduction, 2) transcription, 3) translation, 4) cell cycle regulation, 5) vesicular transport, and 6) production of cytoskeletal elements, cell-adhesion molecules and extracellular matrix components. The data reported are, to our knowledge, the first genetic portrait of osteoblast-like cells cultured on PP. They are relevant to better understanding of the molecular mechanism of bone-PP interaction and as a model for comparing other materials used for bone reconstruction.