Glial fibrillary acidic protein has been firmly established as the predominant component of astrocyte intermediate filaments. It has also been detected immunohistochemically in the glial cells of the enteric nervous system and some Schwann cells in the P.N.S. The molecular identity of this GFAP immunoreactivity in the P.N.S. has so far not been investigated. This study compares GFAP in the C.N.S. and P.N.S. of adult rats both immunochemically and immunohistochemically. Using SDS polyacrylamide gel electrophoresis combined with immunoblotting, and a polyclonal antiserum to brain GFAP, we show that the peripheral GFAP immunoreactivity resides in a polypeptide with a molecular weight of 49 kd, which is identical to that of rat brain GFAP. Furthermore, we find that this GFAP reactivity can be detected immunohistochemically in Schwann cells in a wide variety of nerves in the P.N.S. and in some satellite cells in both sensory and sympathetic ganglia, in addition to enteric glia. The pattern of distribution of GFAP filaments in Schwann cells suggests that, in the nerves surveyed, they may be expressed by most or all non-myelin forming Schwann cells but not by myelin-forming Schwann cells. We also show, using a monoclonal antibody to GFAP (anti-GFAP-3) in both immunohistochemical and immunoblotting studies, that the GFAP found in most peripheral glia is not identical to that of astrocytes since it lacks an antigenic determinant, defined by this monoclonal antibody, which is present in astrocytes. An exception to this finding is seen in the myenteric plexuses where immunohistochemically detectable GFAP is found in some, but not all, of the enteric glia, using the monoclonal antibody. Thus, the results suggest that GFA polypeptides may be a heterogeneous group, that share some common determinants and a common molecular weight, and show a widespread and complex distribution in the glia of both the C.N.S. and P.N.S.