Procalcitonin (PCT) is increasingly recognised as an important diagnostic parameter in clinical evaluation of the critically ill. This prospective study was designed to investigate PCT as a diagnostic marker of infection in critically ill patients with sepsis. Eighty-five adult ICU patients were studied. Four groups were defined on the basis of clinical, laboratory and bacteriologic findings as systemic inflammatory response syndrome (SIRS) (n = 10), sepsis (n = 16), severe sepsis (n = 18) and septic shock (n = 41). Data were collected including C-reactive protein (CRP), PCT levels and Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II scores on each ICU day. PCT levels were significantly higher in patients with severe sepsis and septic shock (19.25 +/- 43.08 and 37.15 +/- 61.39 ng/ml) than patients with SIRS (0.73 +/- 1.37 ng/ml) (P < 0.05 for each comparison). As compared with SIRS patients, plasma PCT levels were significantly higher in infected patients (21.9 +/- 47.8 ng/ml), regardless of the degree of sepsis (P < 0.001). PCT showed a higher sensitivity (73% versus 35%) and specificity (83% versus 42%) compared to CRP in identifying infection as a cause of the inflammatory response. Best cut-off levels were 1.31 ng/ml for PCT and 13.9 mg/dl for CRP. We suggest that PCT is a more reliable marker than CRP in defining infection as a cause of systemic inflammatory response.