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Background: Within a large population of patients seropositive for human immunodeficiency virus type 1 (HIV-1), seven had biopsy specimens that showed foreign body reactions with histologic features different from those seen in non-HIV-1-positive patients., Objective: These cases were reviewed to determine whether there was a specific pattern of response to foreign bodies in HIV-1 infection and whether this pattern was related to the stage of disease., Methods: Biopsy specimens were reviewed to identify ruptured epidermal cysts. These were studied in routine hematoxylin-and-eosin-stained sections and with immunohistochemical stains to characterize the inflammatory infiltrate., Results: The lesions in HIV-1-infected patients contained abundant macrophages with evidence of decreased function and a lack of giant cells., Conclusion: These histologic features suggest an early functional deficit before there is a significant decrease in the number of T4 lymphocytes.