Cardiac abnormalities have been reported in HIV-infected children; however, limited studies have evaluated the histopathologic features or frequency of the coronary vascular lesions that can accompany HIV-related cardiomyopathy. We retrospectively studied 18 children with perinatally-acquired HIV who died between 1986-1995 who had autopsies performed to assess the spectrum of pre-mortem and postmortem cardiac involvement including coronary vasculopathy. Clinical charts, chest radiographs (CXR), echocardiograms (ECHO), ECG studies, and gross and microscopic autopsy findings were reviewed from 10 boys and 8 girls, aged 2 mos to 10 yrs (mean=5 yrs., 2 mos.). Seventeen patients fit CDC class C3, one fit class B3, mean CD4 prior to death-3.6% (range 0-20%). Antiretroviral treatment included: ZDV only (6 pts.), ZDV + ddl or ddc (5 pts), or none (7 pts). Cardiac studies in vivo identified abnormalities in 13 pts. (72%) including ECG changes in 7/12 pts. and cardiomegaly on CXR in 4/18; ECHO revealed left ventricular dilatation (6/14 pts), decreased systolic function (5/14 pts), or right ventricular hypertrophy(1/14 pt). Four patients had symptomatic cardiac dysfunction; all had cardiomegaly. At autopsy, 16 pts (89%) demonstrated varying degrees of cardiomegaly, interstitial fibrosis, and/or CV. Vascular lesions were present in 10 patients characterized by smooth muscle and intimal proliferation with moderate to severe luminal stenosis; four patients had >50% stenosis of at least one epicardial vessel. Immunolocalization studies revealed angiogenic inducers such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in the proliferating neointima of the coronary vessels in 5/5 patients with CV studied vs. 0/6 without CV. Eight patients with CV showed moderate to severe interstitial fibrosis, suggestive of chronic ischemia. CMV coinfection was sought in 13/18 patients, seven with CV and six without CV; among these 13 patients, CMV was present in four, all of whom had CV (P=0.02). In conclusion, unrecognized coronary vasculopathy is common in children with end-stage HIV infection, and may be related to CMV coinfection and/or presence of angiogenic growth factors.