1. Infection in the neonatal period is difficult to diagnose and is a significant cause of morbidity and mortality in preterm infants. 2. We investigated prospectively the predictive value of plasma measurement of bacterial endotoxin (lipopolysaccharide), tumour necrosis factor-alpha, interleukin-6, interleukin-8, intercellular adhesion molecule-1 and C-reactive protein in 60 consecutive newborn infants suspected of having neonatal infection. Plasma samples were taken at the time of acute clinical deterioration. Sixty-two cord blood samples were studied as controls taken at elective Caesarean section. 3. Forty-three infants had confirmed infections, 25 with positive blood cultures. Tumour necrosis factor-alpha and bacterial endotoxin levels were not significantly elevated over controls, whereas interleukin-6, interleukin-8 and intercellular adhesion molecule-1 levels were all significantly increased in the infected group compared with controls (all P < 0.001). 4. Increased plasma intercellular adhesion molecule-1 levels were a highly sensitive (88%) indicator of clinical infection and were independent of C-reactive protein. Use of these two assays in combination improved the diagnostic sensitivity to 95% and gave a negative predictive value of 97%. addition of interleukin-6 or interleukin-8 measurements failed to further significantly enhance the prediction of infection. 5. Measurement of intercellular adhesion molecule-1 level may have a clinical role in rapidly confirming, or predicting, the likely diagnosis in cases of suspected neonatal infection.