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Integrin alpha(6) beta(4) is expressed in human peripheral nerves, but not in the central nervous system. This integrin heterodimer has previously been found in perineural fibroblast-like cells and in Schwann cells (SCs), which both assemble a basement membrane but do not form hemidesmosomes. We show here that in SCs, which had formed a myelin sheath, alpha(6) beta(4) was enriched in the proximity of the nucleus, at Ranvier paranodal areas and at Schmitt-Lanterman clefts; alpha(6) beta(4) was also found at the grooved interface between small axons and non-myelinating SCs. Immunoprecipitation of human peripheral nerves, in combination with Western blotting showed that beta(4) is associated with the alpha(6A) subunit. Northern blot analysis of human peripheral nerves showed a single beta(4) transcript of 6 kb. Using the reverse transcriptase polymerase chain reaction, we detected two mRNA species, one for the most common (-70, -53) form of beta(4) and the other encoding the (+53) variant of beta(4). Cultured SCs were devoid of alpha(6) beta(4) but expressed alpha(6) beta(1), indicating that SCs lose beta(4) expression when contact with neurons is lost. Thus, resting SCs in contact with axons express alpha(6A) in combination with beta(4), irrespective of myelin formation. We suggest that alpha(6) beta(4) expressed in SCs plays a role in peripheral neurogenesis.