We previously reported that a protein which has immunological cross-reactivity with and a molecular weight similar to dystrophin, the Duchenne muscular dystrophy (DMD) gene product, is expressed on the muscle cell membrane (Tanaka et al. 1989b). To examine if this is the translation product of the autosomal transcript with homology to dystrophin mRNA identified by Love et al. (1989), we raised an antibody (PDRP) against a synthetic peptide corresponding to the putative protein (DRP) and examined its expression and cellular localization in human and murine skeletal muscle samples. In immunoblotting, PDRP stained a band with a similar molecular weight to dystrophin in samples from DMD and Becker muscular dystrophy (BMD) patients and control (non-DMD/BMD) human. PDRP was expected not to cross-react with dystrophin because the antigenic peptide was not homologous to dystrophin. In fact, PDRP did not cross-react with dystrophin present in a BMD patient. Immunohistochemically, PDRP stained the muscle cell membrane in samples from DMB and BMD patients and from mdx mice. Only a slight staining was observed in muscles from control human and wild type mice. Our results confirm the presence of DRP in human and murine skeletal muscles, and further demonstrate that it is localized on the cell membrane. The abundance of DRP in dystrophin deficient muscles might be related to some compensatory mechanisms.