We described the development of prolonged disseminated cutaneous herpes zoster in two patients with acquired immunodeficiency syndrome. Both patients developed hyperkeratotic, verrucous lesions that progressed despite acyclovir therapy. The biopsy specimens were typical of herpes infection. The development of acyclovir-resistant varicella-zoster virus during therapy was suspected clinically in the first patient and documented in vitro in the second patient. The inability to mount an effective cell-mediated immune response contributed to the prolonged course of cutaneous zoster in our patients. The hyperkeratotic nature of the skin lesions may reflect their chronic nature. Treatment with inadequate doses of acyclovir, allowing viral persistence and the selection of resistant strains of virus, may also be implicated. We recommend prolonged high-dose intravenous acyclovir therapy in the initial management of herpes zoster in patients with acquired immunodeficiency syndrome.