A 35-year-old male former abuser of i.v. drugs, who was known to be human immunodeficiency virus (HIV) positive for 3 years, was found to have osteonecrosis (ON) involving both internal femoral condyles and humeral heads. No causes other than the HIV were evident. Joint irrigation, applied by means of an irrigation-withdrawal system, provided some relief and functional improvement. A literature search for references to the potential association of osteonecrosis with HIV infection showed a number of reports and three with multiple sites, suggesting that osteonecrosis can be considered a manifestation of HIV infection. The underlying pathogenic mechanisms remain obscure but are proposed to be related to immune alterations caused by HIV infection itself. HIV should be considered an etiological factor in patients with a diagnosis of multiple ON. Irrigation of the accessible regions of the joints involved may be an effective therapeutical choice to help control the symptoms.