Indinavir-associated adverse dermatologic reactions are rare but do occur. A 39-year-old man who was positive for the human immunodeficiency virus and had no known allergy, developed an erythematous, maculopapular eruption several hours after switching to a new triple-drug regimen consisting of stavudine, didanosine, and indinavir. The eruption completely resolved 2 weeks after he discontinued the antiretroviral combination. To preserve future treatment options, the patient was sequentially rechallenged with each agent and confirmed indinavir as the cause. The patient tolerated and responded to a new combination of stavudine, didanosine, and nelfinavir. The rapid onset of the adverse reaction suggested that it might have been immunoglobulin-E mediated. No cross-sensitivity between indinavir and nelfinavir was apparent.