The cell surface glycoprotein CD9 is a member of a group of proteins known as the "tetraspan" or "transmembrane 4 superfamily." Previous work with non-neural cells has shown that CD9 associates in cis with integrins and small GTP-binding proteins on the cell surface. To extend our recent findings showing that perturbation of CD9 alters Schwann cell adhesion, proliferation, and migration, as well as neurite outgrowth in sympathetic neurons, we have searched for CD9-associated proteins in S-16 Schwann cells. We demonstrate here that CD9 is specifically coprecipitated from S-16 cell extracts by antibodies against integrins alpha 3, alpha 6, and beta 1. In addition, double immunofluorescence labeling and co-capping experiments indicate that CD9 is specifically co-localized with these integrins on the cell membrane of S-16 Schwann cells.