This study assessed the value of routine CRP measurements to discriminate between bacterial and viral lower respiratory tract infection (LRTI) in HIV-1-infected and -uninfected children. A total of 570 children, prospectively enrolled, were categorised into four aetiological groups, as follows: (i) bacteraemic pneumonia (n = 50), (ii) respiratory virus-associated LRTI (n = 146), (iii) bacteraemic and respiratory virus-associated (mixed) LRTI (n = 10), and (iv) LRTI of undetermined aetiology (n = 364). The discriminative ability of threshold CRP values was evaluated, and values predicting bacteraemic pneumonia were used to construct receiver-operating characteristic (ROC) plots. Median CRP values were significantly higher in bacteraemic pneumonia (195 mg/L, p < 0.0001), and threshold CRP values ranging from 10 to 100 mg/L differentiated bacteraemic from virus-associated LRTI (p < 0.0001). The discriminative ability of CRP values assessed by ROC plots in pneumonia is 80%, and CRP > or = 10 mg/L identified 90% of all bacteraemic pneumonia. In HIV-1 infection, median CRP values were significantly higher in bacteraemic pneumonia (200 mg/L) but correlated with levels in uninfected children, irrespective of LRTI aetiology. Although CRP responses are significantly different in bacteraemic and virus-associated LRTI, the considerable overlap between these aetiological groups hinders selection of threshold CRP values that are clinically useful in differentiating bacteraemic from virus-associated LRTI pneumonia.