The phenotypic abnormalities in the medial region of the developing mandible in mice carrying compound mutations in Prx1 and Prx2 provide direct evidence that Prx genes are components of a poorly characterized signaling pathway involved in mandibular outgrowth and morphogenesis. The mandibular processes of the neonate double mutant mice are shortened, fused at the midline, lack the midline symphysis and have only a single or no incisors. Objectives: To gain insight into underlying mechanisms leading to shortened mandibular processes in Prx1;Prx2 double mutants. Methods: Cell proliferation and cell death in the mandibles of these mutants were compared to those of controls. Cell proliferation and cell survival were assayed by anti-phosphorylated histone 3 immunohistochemistry and by TUNEL assays on tissue sections respectively. Results: Comparison of width and length of the mandibles showed that at E10.5 double mutant mandibles were approximately 82% and 84% of the size of the controls respectively. The number of proliferative cells in the mandibles of double mutants (226±86/mm2) was significantly lower than that in the controls (479±87/ mm2). There was also increase in the number of apoptotic cells in the medial and lateral regions of the mandibles of double mutants as compared to the controls. Conclusion: The reduced size of the mandible of Prx1;Prx2 double mutants is related to both decreased cell proliferation and increased cell death indicating that Prx gene products are required for maintenance (proliferation and/or survival) of mandibular mesenchyme. Supported by NIH grant DE08682.