To determine the comparative efficacy of tap water iontophoresis to iontophoresis with the anticholinergic glycopyrrolate, we undertook a single-blinded right-left comparison study in 20 patients with palmoplantar hyperhidrosis. Most patients had their palms treated and one patient had the soles treated. We compared the duration of symptom relief following iontophoresis with glycopyrrolate unilaterally to iontophoresis with glycopyrrolate bilaterally. Patients filled in daily efficacy assessment cards. Each palm was rated as 'dry', 'slightly wet', 'moderately wet' or 'very wet'. Following treatment with unilateral tap water iontophoresis, unilateral glycopyrrolate and bilateral glycopyrrolate, patients reported hand dryness for a median of 3, 5 and 11 days, respectively. As the data was paired, treatment differences were analysed using a sign-rank test. Bilateral glycopyrrolate was superior to both unilateral glycopyrrolate and tap water in most patients. Unilateral glycopyrrolate was superior to tap water in most patients. All differences between groups were found to be statistically significant. We postulate that the increased efficacy of bilateral glycopyrrolate when compared with unilateral glycopyrrolate relates to its systemic absorption. We conclude that glycopyrrolate iontophoresis is more effective than tap water iontophoresis in the treatment of palmoplantar hyperhidrosis and that glycopyrrolate iontophoresis has both local and systemic effects on perspiration.