Background: A novel type of acquired partial lipodystrophy resulting from chronic treatment with HIV-1 protease inhibitor drugs has recently been described. Objective: We studied the clinical and histopathologic features of a series of patients with HIV-1 protease inhibitor–associated lipodystrophy to evaluate the frequency of associated abnormalities. Methods: The study group consisted of 14 consecutive HIV-infected patients receiving treatment with HIV-1 protease inhibitors, who experienced partial lipodystrophy. Clinical (including anthropometric data) and histopathologic findings, as well as biochemical and virologic data, were evaluated. Results: A significant loss of fat in the face and extremities was associated with fat deposition on the abdomen, breast, and dorsocervical fat pad. Central obesity was frequently present. Histopathologic features disclosed a peculiar type of involutional lipodystrophy. Hypertriglyceridemia was detected in 78.5% of patients. Low serum levels of cholesterol–high-density lipoprotein and high cholesterol–very-low-density lipoprotein were noted. Hyperglycemia, hypercholesterolemia, or hyperinsulinemia were occasionally detected. Conclusion: HIV-1 protease inhibitor–associated lipodystrophy represents a new entity with peculiar clinical and histopathologic features. Metabolic associated abnormalities may imply a risk of future atherogenic complications. (J Am Acad Dermatol 2000;42:193-8.)