Schwann cells within the distal portion of a transected nerve undergo a series of poorly understood events in response to injury and loss of axonal contact. These events may influence the regeneration of PNS neurons. In this study we examined the alteration of antigens located in the basal lamina, plasma membrane and cytoplasm of Schwann cells within the distal nerve stump: (a) after a complete transection of the sciatic nerve, and (b) subsequent to reestablished contact between regenerating axons and dedifferentated Schwann cells separated from contact with neurons. Visualization of laminin and heparan sulphate proteoglycan molecules at various intervals after nerve transection always revealed intact basal lamina channels. In response to loss of axonal contact, vimentin expression by Schwann cells within the distal nerve stump increased, becoming a predominant intermediate filament protein of the cytoskeleton while glial fibrillary acid protein (GFAP) expression decreased. This reversal in the prominence of intermediate filament proteins was maintained until the onset of axonal reinnervation, at which point expression of GFAP increased and vimentin decreased. Expression of the Schwann cell plasma membrane associated protein, C4, closely mimicked GFAP expression during axon degeneration and subsequent reinnervation. In the normal uninjured nerve, tissue plasminogen activator (tPA) and S-100 were localized in the region near the Schwann cell-axon interface and the outer Schwann cell plasma membrane. In response to loss of axonal contact, the S-100 and tPA immunoreactivity associated with the Schwann cell-axon interface was lost while that localized around the outer Schwann cell plasma membrane remained unchanged. The results of this study demonstrate that Schwann cells modulate a portion of their antigenic repertoire in response to a loss of axonal contact and after contact with regenerating axons.