BACKGROUND: Lipodystrophies are rare cutaneous disorders characterized by the symmetrical loss of subcutaneous fat from the body surface. The cause of lipodystrophy is not known, but a possible genetic predisposition is likely and either overt diabetes mellitus or insulin resistance are often associated. DESIGN AND METHODS: Case study. PATIENTS: Eight patients who developed either partial or generalized lipodystrophy after protease inhibitor therapy. RESULTS: In all eight patients lipodystrophy occurred after 2-12 months of starting indinavir and was not preceded by weight loss or inflammatory skin disease. Short-term follow-up after withdrawal of therapy showed no change in the patients' appearance. One patient developed glycosuria as lipodystrophy became manifest. In three cases glucose tolerance test was performed revealing a high level of insulin between the first and third hour of loading. CONCLUSIONS: In our view, lipodystrophy is an unwanted side-effect of protease inhibitor therapy causing noticeable disfigurement.