Thrombotic microangiopathy (TMA) can occur during the course of human immunodeficiency virus (HIV) infection. Clinical and pathological data for 29 patients with TMA and HIV infection were recorded. In a retrospective case-control study, we analyzed the link between opportunistic infections or drug therapies and TMA. Twenty-five patients (mean CD4+ cell count +/- SD, 71.9 +/- 18.3/mm3) had renal impairment, and four had neurological dysfunction. In one-half the cases, the disease was progressive with isolated fragmentation anemia appearing several months before the clinical symptoms. The diagnosis of TMA was confirmed by histological examination of kidney biopsy specimens (18 cases). Endothelial cytomegalovirus (CMV) inclusions were associated with TMA in nine of 18 cases, whereas histological examination did not detect CMV in any control specimens (P < .001). The case-control study demonstrated a link between TMA and clinical CMV infection (odds ratio, 3.9; 95% confidence interval, 1.1-14). We conclude that TMA is a late complication of HIV infection and can be associated with systemic CMV infection in this setting.