Rates of infection by the human immunodeficiency virus (HIV) have been increasing rapidly in South Africa over the last decade. This study documents the changes over time in prevalence of HIV infection amongst hospitalized children, and its effects on the profile of disease and in-hospital mortality over the period 1992-1997. Admissions to the paediatric medical wards between January 1992 and April 1997 were obtained from the routine computerized database held in the Department of Paediatrics at Chris Hani Baragwanath Hospital. HIV tests were performed on clinical indications only. Over the study period there were 22,633 admissions involving 19,918 children. Total annual admissions increased by 23.6% between 1992 and 1996. Prevalence of HIV infection increased from 2.9% in 1992 to 20% in 1997. HIV-infected children had a younger age distribution, longer median length of stay and more readmissions (p < 0.001) compared with HIV-negative and untested children. HIV-infected children accounted for the increased number of admissions for pneumonia, gastro-enteritis, malnutrition and tuberculosis, and the rise in in-hospital mortality by 42% from 4.3% in 1992 to 6.1% in 1997. Paediatric HIV infection has changed the profile of paediatric admission diagnoses and increased in-hospital mortality in the relatively short time between 1992 and 1997. Over the same period, HIV-negative children showed declining rates of malnutrition, vaccine-preventable diseases and admission to the intensive care unit.