In three patients, a 36-year-old HIV seropositive homosexual man and two women aged 35 and 59 years who had acquired HIV infection through heterosexual contact, signs of lipodystrophy developed after prolonged anti-HIV triple therapy. The observed syndrome is seen after prolonged use of HIV protease inhibitors: it is characterized by peripheral fat wasting, central fat accumulation, hyperlipidaemia and insulin resistance. Typically the subcutaneous fatty tissue disappears resulting in prominent zygomata, veins and muscles and thinning of extremities and buttocks. In addition to abdominal fat accumulation, there have been reports on the occurrence of a dorsocervical fat pad, the so-called buffalo hump. Lipodystrophy caused by protease inhibitors is a risk factor for cardiovascular disease. Recognition of the syndrome is essential for adequate follow-up and possible treatment.