The World Health Organization (WHO) clinical case definition for paediatric AIDS was tested during a 1-month period on 221 consecutive hospitalized children in Kigali, Rwanda. Relevant clinical features not included in the WHO case definition were also evaluated. Thirty-four out of the 221 children (15.4%) were HIV seropositive. Although the specificity of the WHO case definition was high (92%), the sensitivity and the positive predictive value (PPV) were low (41 and 48%, respectively). The following individual signs had a PPV at least equal to the complete WHO case definition: chronic diarrhoea (47%), respiratory distress secondary to lower respiratory tract infection (50%), oral candidiasis (53%), parotitis (67%), generalized lymphadenopathy (88%), and herpes zoster infection (100%). When logistic regression analysis was done on the nine variables included in the WHO case definition, confirmed maternal infection was the best predictive variable for HIV seropositivity in children (P less than 10(-5). We further excluded the serological status of the mother from the analysis and performed a stepwise logistic regression analysis on the 18 clinical signs and symptoms for which information had been collected. Those signs and symptoms contributing the most to the regression were: respiratory distress, chronic diarrhoea and generalized lymphadenopathy. Based on these findings, we propose a simplified clinical case definition for paediatric AIDS in Africa with better sensitivity, specificity and PPV than the WHO case definition. Further work is needed using this approach to develop case definitions useful for epidemiological surveillance and for case management.The World Health Organization (WHO) clinical case definition for pediatric acquired immunodeficiency syndrome (AIDS) was evaluated over a 1-month period in 221 consecutive hospitalized children in Kigali, Rwanda. The median age of the children studied was 18 months (range, 1 month-14 years); 55% were boys. 34 (15%) of these 221 children were seropositive for the human immunodeficiency virus (HIV). Although the specificity of the WHO case definition was high (92%), its sensitivity was only 41% and the positive predictive value was 48%. The following individual signs had a positive predictive value at least equal to the complete WHO case definition: chronic diarrhea (47%), respiratory distress secondary to lower respiratory tract infection (50%), oral candidiasis (53%), parotitis (67%), generalized lymphadenopathy (88%), and herpes zoster infection (100%). Logistic regression analysis on the 9 variables included in the WHO case definition indicated that confirmed maternal HIV infection was the best predictive variable for HIV seropositivity in children. When maternal serological status (rarely available in Rwanda) was excluded from the analysis and a stepwise logistic regression analysis was performed on the 18 clinical signs and symptoms for which data had been collected, respiratory distress, chronic diarrhea, and generalized lymphadenopathy emerged as the signs contributing the most. On the basis of these findings, a simplified clinical case definition of pediatric AIDS is proposed for settings where resources are limited and HIV seroprevalence is high. According to this definition, pediatric AIDS should be suspected in a child presenting with 1 or both of the following clinical signs: respiratory distress secondary to lower respiratory tract infection and/or generalized lymphadenopathy. However, it is necessary to test this definition on a larger scale in Central Africa and in other parts of the world with different rates of HIV seroprevalence.