The lipodystrophy syndrome (LDS) is a growing problem in human immunodeficiency virus (HIV)-positive patients treated with highly active antiretroviral therapy (HAART). It is characterized by alterations of body composition and metabolic abnormalities. The goal of the study was to investigate attitudes toward health condition, well-being, and individual appearance in relation to LDS. Outpatients between July and October 2000 in an HIV-specialized unit at the University Hospital of Düsseldorf, Germany, underwent clinical evaluation and received a standardized written questionnaire. Of 389 patients eligible for analysis, 313 patients returned completed questionnaires (response rate, 80.5%). LDS was observed in 37.7%; the predominant manifestation was lipoatrophy of the face (32.9%). Individuals with and without LDS did not differ significantly in their attitude to the quality of their health condition and the amount of disturbance of their well-being by HIV infection. Participants with LDS felt recognizable as HIV-positive by physical appearance in 30.1%, compared to 18.3% in patients without LDS (p = 0.027). This difference became more pronounced after adjustment for gender, age, stage of disease, CD4 cell count, and duration of HAART (odds ratio, 2.04, 95%-confidence interval [CI] 1.09-3.84). In conclusion, LDS does not seem to disturb the general attitude toward health condition and well-being. However, patients presenting with lipodystrophy are about twice as likely to feel recognizable as HIV-positive by their physical appearance. LDS may thus be perceived as a characteristic mark of being HIV-positive by affected persons. A stigmatizing effect and social disadvantages may be the consequences.