Recalcitrant pruritus is a hallmark of lichen simplex, a localized variant of atopic dermatitis. Acetylcholine has been demonstrated to mediate pruritus in atopic dermatitis. This open pilot study was done to determine the therapeutic effect of blocking acetylcholine release with botulinum toxin A in highly pruritic lichen simplex. Botulinum toxin A (Dysport) was injected intradermally into 5 circumscribed lichenoid lesions in 3 patients suffering from recalcitrant pruritus. No corticosteroids or any other specific topical therapy was administered. Pruritus subsided within 3 to 7 days in all 3 patients. Within 2 to 4 weeks all lesions cleared completely. No recurrences were noted over a 4-month follow-up. In one patient lichen simplex developed on the contralateral shin, which responded equally to a subsequent injection. We concluded that lichen simplex-associated pruritus can be overcome by intradermal botulinum toxin A injection. Acetylcholine appears to be a dominant pruritic mediator in this condition. (J Am Acad Dermatol 2002;46:617-9.)