Gene targeting experiments have defined that the homeobox gene Prx1 is essential for normal craniofacial, limb, and vascular development. Although its RNA expression pattern is well established, Prx1 protein expression in the developing embryo has not been examined. A novel Prx1 antibody was produced to define the normal Prx1 protein expression pattern in the developing mouse embryo. In craniofacial and limb mesenchyme, Prx1 protein expression is consistent with previously published data on RNA localization. However, a remarkable discrepancy was found in cardiac tissue. Prx1 protein is undetectable in the murine embryonic and adult heart, despite the presence of Prx1 transcripts. These data demonstrate that Prx1 expression is posttranscriptionally regulated. This discrepancy between the presence of Prx1 transcript and the absence of detectable protein was also observed in embryonic chick heart, suggesting conservation of the regulatory mechanism in vertebrates. This observation provides a new explanation of why the Prx null mice lack cardiac malformations.