A prospective study of 250 consecutive neonatal admissions to a regional perinatal referral centre and of 10 additional consecutive cases with culture-proven neonatal septicaemia was undertaken. Quantitative C-reactive protein (CRP) determination, white cell count and differential were performed on blood samples obtained from all babies on admission, as well as 10–14 h and 22–26 h later. Using clinical signs, chest X-rays, blood cultures, tracheal aspirates obtained within 4 h of delivery and an abnormal immature/total neutrophil ratio (I/T), infected babies were defined as belonging to one of the following groups: (1) Culture-proven septicaemia (n=19); (2) Clinical septicaemia (n=35); (3) Congenital pneumonia (n=28). The sensitivity, specificity, positive and negative predictive value of CRP were calculated for each sampling time and patient group. No baby had a rise in CRP (>6mg/l) before an abnormal I/T ratio was first detected. A delayed rise in CRP concentration in the majority of infected babies occurred approximately 12–24 h after the abnormal I/T ratio was first detected. The overall specificity of a CRP level of ≥10 mg/l remained approximately constant (97%–94%) while sensitivity increased from 22%–61% with increasing time after admission. The same pattern emerged if each patient group was considered separately. The positive predictive value for a CRP level of ≥10mg/l 22–26 h after admission was 83% and the negative predictive value 82%. CRP had no value in the early diagnosis of neonatal infection. Its main role lies rather in the exclusion or confirmation of infection 24 h after the first clinical suspicion.