We have previously demonstrated (J. Neurosci., 14: 1309-1319) that Schwann cells (SCs) isolated from adult human peripheral nerve in tissue culture and then transplanted into an immune-deficient rat can enhance axonal regeneration and myelinate regenerating peripheral axons. We have now (a) compared the capacity of both primary and expanded populations of cultured human SCs to form myelin around regenerating mouse axons when transplanted into a gap within the sciatic nerve of severe combined immunodeficiency (scid) mice and (b) also compared the myelinating capability of these cultured SCs to their counterparts in the native human peripheral nerve xenograft. Schwann cells were isolated from adult human peripheral nerve. Semipermeable guidance channels were filled with a 30% Matrigel solution mixed with either primary human SCs or human SCs expanded with mitogens both at a density of 120 million cells/ml. These channels or a human peripheral nerve xenograft were implanted within a 5-mm gap in the transected sciatic nerve of the scid mice and analyzed after a period of 6 weeks. The presence of human myelin segments was confirmed in both the guidance channels containing human SCs and the xenografts by immunostaining with a monoclonal antibody (592) which specifically recognizes a prominent myelin component, P0, in the human but not in the mouse. Within both the guidance channels and the xenografts there was an invasion of the transplant by host SCs which went on to form myelin around regenerating mouse axons. In this report, we also demonstrate that human SCs that have been expanded in culture with mitogens are capable of forming myelin after transplantation in this experimental paradigm.