We present a 35-year-old patient with acquired immunodeficiency syndrome who had demodicidosis on his face, characterized by multiple papules and papulopustules, associated pruritus, numerous mites on skin-surface biopsy and in biopsy specimens, and rapid response to topical treatment with permethrin. It seems likely that Demodex infestation does not manifest unless local or systemic immune function is altered, leading to the proliferation of the organism and subsequent disease.