Carpal tunnel syndrome (CTS) has become the industrial epidemic syndrome of the decade and its incidence is continuing to rise. Because of public awareness, CTS is being diagnosed much earlier in the course of the disease. Iontophoresis of dexamethasone sodium phosphate has been used for years in the treatment of many musculoskeletal inflammatory disorders and clinicians have reported using this modality in the treatment of CTS. Iontophoresis is a method of transdermal administration of ionized drugs in which electrically charged molecules are propelled through the skin by an external electrical field. However, conditions of treatment and evaluation have not been standardized. A prospective, nonrandomized study utilizing a standardized treatment protocol incorporating wrist splinting with nonsteroidal antiinflammatory medications and iontophoresis of dexamethasone sodium phosphate revealed a success rate comparable with splinting plus injection of dexamethasone into the carpal tunnel space. In a 6-month follow-up of 23 cases (hands) of early-mild CTS, 4 of 23 hands (17%) were successfully treated with splints plus nonsteroidal antiinflammatory medications alone. Of those that failed this treatment program and chose to proceed with iontophoresis of dexamethasone, 11 of 19 hands (58%) had a positive response rate to iontophoresis, leaving a combined failure rate (failing both splints, nonsteroidal antiinflammatory medications and iontophoresis) of 35%. Iontophoresis may become an alternative become an alternative to steroid injections to the carpal tunnel region if further studies substantiate these findings. It provides an excellent complication and side-effect profile compared with other methods of delivering dexamethasone. No complications occurred (including no significant elevation of serum glucose in insulin-dependent diabetics).