Three hundred and nine septic screens were performed on 123 consecutively admitted infants of < 30 weeks gestation. As part of the septic screen, serial quantitative measurements of C-reactive protein (CRP) were performed daily until discontinuation of antibiotic therapy. Complete blood counts were performed daily for the first 2 days of each septic episode. The babies had a mean birth weight of 1035.8 g s.d. 273.2 and a mean gestational age of 27 weeks s.d. 1.8. A CRP level of 10 mg/L or above was considered abnormal. Subsequently the receiver operator characteristic curve for CRP was constructed to demonstrate the ideal cut off value. Of the 309 septic screens, there were 51 instances of proven sepsis and 39 instances of deep culture negative sepsis. In the remaining 219, a diagnosis of proven or deep culture negative sepsis could not be made. On the first day of the septic episode CRP showed a sensitivity of 62.7%, specificity of 87.2% and negative predictive value of 92.2% for proven sepsis. There was a significant increase in the sensitivity (90.2%) and negative predictive value (97.7%) of CRP with a specificity of 80.6 when both day 1 and 2 estimations were combined. We conclude that when the CRP is elevated on day 1 and/or day 2, the diagnosis of sepsis is extremely likely and when the CRP is within normal limits on days 1 and 2 of the septic episode, neonatal sepsis can be confidently excluded and antibiotic therapy ceased.