A 30-year-old bisexual man who was infected with human immunodeficiency virus (HIV) and had a history of anaphylaxis to penicillin developed lues maligna, or ulceronodular secondary syphilis. Therapy with parenteral erythromycin failed, and he was subsequently treated with ceftriaxone following penicillin desensitization. A review of the English-language literature identified 14 cases of lues maligna reported between the early 1900s and 1988. From 1989 to 1994, an additional 12 cases (including the current case) were reported. Of those 12 cases, 11 occurred in patients who either were infected with HIV or were at high risk for HIV infection. Patients infected with HIV may be at increased risk of developing this severe form of secondary syphilis. Lues maligna should be considered in the differential diagnosis of HIV-infected patients who present with ulceronodular lesions.