Since 1985 a physical and instrumental cardiac study was carried out in 41 children with perinatal HIV-1 infection in order to assess the prevalence and natural history of cardiac involvement. Children were followed for 66 (range 8-109) months; eight of 41 died of HIV-1 related diseases. The cumulative proportion of children with cardiac manifestations at age of seven years was 14.9% (95% CI: 4.9-31.5%). Cardiac abnormalities were detected in eight of 41 patients (19.5%) and were more significantly (p=0.003) recorded in children who died of HIV-1 related diseases (five of eight, 62.5%). Left ventricular systolic function was normal in most patients during the follow-up and did not depend on zidovudine treatment. Two patients had a severe dilated cardiomyopathy and underwent subsequently a stable regression as far as the clinical and instrumental frame was concerned. Only one patient died because of cardiac disease. We conclude that in our group ofperinatally HIV- 1 infected children, cardiac involvement is relatively rare, represents a late complication compared to other related HIV-1 diseases and occurs in advanced stages of illness. Cardiac disease is therefore a hallmark of poor prognosis, but is rarely the ultimate cause of death.