The sigma-1 (sigma(1)) receptors can bind different psychotropic drugs and have been implicated in schizophrenia, depression and dementia. The cloning of the sigma(1)-receptor has allowed to obtain specific antibodies and, in a recent immunohistochemical study, we demonstrated that, in addition to neurons, the sigma(1)-receptor is located in oligodendrocytes [Brain Res. 961 (2003) 92.]. In the present study using in vivo and in vitro techniques, we demonstrate the localization of the sigma(1)-receptor in Schwann cells. Double immunofluorescence studies showed that sigma(1)-receptor co-localized with S100 protein, a specific marker of Schwann cells, in both rat sciatic nerve Schwann cells and Schwann cells in cultures. The sigma(1)-receptor immunoreactivity was seen in the cytoplasm and paranodal region formed by these cells, but not in myelin itself. The presence of sigma(1)-receptor in oligodendrocytes and Schwann cells is discussed on the basis on recent findings involving this receptor in lipid metabolism, compartmentalization and transport to the plasma membrane, thus suggesting a role for sigma(1)-receptor signaling in myelination.