Background: Severe palmar hyperhidrosis is a chronic disease, resistant to conventional therapy. Botulinum toxin inhibits sweat production by blocking release of acetylcholine from presynaptic membranes. Objective: Our purpose was to evaluate the short- and long-term effectiveness of botulinum toxin therapy in treatment of palmar hyperhidrosis. Methods: Four patients with severe palmar hyperhidrosis were treated with subepidermal injections of botulinum toxin. Fifty injections, 2 mouse units each, were used in each palm. Regional nerve blocks of the median and ulnar nerves were performed before the procedure. Patients were observed for 12 months after treatment. Results: Botulinum toxin injections significantly reduced sweat production in the treated areas of the palms. Anhidrosis lasted for 12 months in one patient, 7 months in two patients, and 4 months in one patient. Mild weakness of the thumb lasting 3 weeks occurred in one patient. No other side effects were observed. Conclusion : Botulinum toxin provides an effective, safe, and long-lasting alternative therapeutic modality for treatment of severe palmar hyperhidrosis. Additional studies are needed for optimization of the technique.(J Am Acad Dermatol 1998;38:227-9.)