In order to study the factors that govern the expression of sodium channel α‐, β1‐ and β2‐subunits, the influence that Schwann cells (SC) exert in the expression of sodium channels in DRG neurons was examined with in situ hybridization, immunocytochemistry, and patch clamp recording. The expression of sodium channel α‐, β1‐, and β2‐subunit mRNAs in DRG neurons isolated from E15 rats cultured in defined medium in the absence (control) or presence of SC, or in SC‐conditioned medium, was examined with isoform‐specific riboprobes for sodium channel α‐subunits I, II, III, NaG, Na6, hNE/PN1, SNS, and β1‐ and β2‐subunits. DRG neurons cultured in the presence of SC displayed a significant (P < 0.05) increase in the hybridization signal for NaG, Na6, SNS, and Naβ2 mRNAs in comparison to control DRG neurons. In contrast, in SC‐conditioned medium, only the hybridization signal for SNS mRNA was significantly increased. The upregulation of sodium channel mRNAs in DRG neurons co‐cultured with SC was paralleled by an increase in sodium channel immunoreactivity of these cells. An increase in the mean sodium current density in DRG neurons in the presence of SC was also observed. These results demonstrate that a SC‐derived factor selectively upregulates sodium channel α‐ and β‐subunit mRNAs in DRG neurons isolated from E15 rats that is reflected in an increase in functional sodium channels in these cells. This culture system may allow elucidation of the SC factor(s) that modulate the expression of sodium channels in DRG neurons. GLIA 21:339–349, 1997. © 1997 Wiley‐Liss, Inc.