OBJECTIVE To assess the clinical significance of peripheral eosinophilia in HIV-infected individuals. METHODS In a retrospective case-control study we compared 42 HIV-infected patients (cases) with peripheral eosinophilia (absolute eosinophil count > 500 cells/mm3) with 84 HIV-infected controls without eosinophilia. Cases were matched to controls by date, and by CD4 cell count. Data on clinical parameters possibly associated with eosinophilia were collected and compared among cases and controls. RESULTS Eosinophilia was seen in patients with late-stage HIV disease (median CD4 cell count of 26 cells/mm3). Cases were more likely to be black (52% versus 18%, P = 0.0001), have pruritus (50% versus 20%, P = 0.002), and have a physician-documented rash (76% versus 52%, P = 0.02). Specific cutaneous diagnoses that were more prevalent in cases versus controls were eosinophilic folliculitis (24% versus 1% P = 0.0001), atopic dermatitis (14% versus 1%, P = 0.01), and prurigo nodularis (7% versus O, P = 0.07). Other parameters commonly associated with eosinophilia such as allergic reactions, parasitic infection, malignancy, and adrenal insufficiency were not found at higher incidence in cases. CONCLUSIONS Eosinophilia in AIDS patients is associated with cutaneous disease, but not with other conditions commonly associated with eosinophilia including parasitic infections, allergic reactions, or malignancy. Extensive work up for asymptomatic eosinophilia in patients with AIDS and cutaneous disease is not warranted.