Objective: To assess the use of procalcitonin (PCT) for the diagnosis of infection in a medical ICU. Design: Prospective, observational study. Patients: Seventy-seven infected patients and 24 patients with systemic inflammatory response syndrome (SIRS) due to other causes. Seventy-five patients could be classified into sepsis (n = 24), severe sepsis (n = 27) and septic shock (n = 24), and 20 SIPS patients remained free from infection during the study. Plasma PCT and C-reactive protein (CRP) levels were evaluated within 48 h of admission (day 0), at day 2 and day 4. Results: As compared with SIPS, PCT and CRP levels at day 0 were higher in infected patients, regardless of the severity of sepsis (25.2 +/- 54.2 ng/ml vs 4.8 +/- 8.7 ng/ml; 159 +/- 92 mg/l vs 71 +/- 58 mg/l, respectively). At cut-off values of 2 ng/ml (PCT) and 100 mg/l (CPP), sensitivity and specificity were 65 % and 70 % (PCT), 74 % and 74 % (CRP). PCT and CPP levels were significantly more elevated in septic shock (38.5 +/- 59.1 ng/ml and 173 +/- 98 mg/l) than in SIPS (3.8 +/- 6.9 ng/ml and 70 +/- 48 mg/l), sepsis (1.3 +/- 2.7 ng/ml and 98 +/- 76 mg/l) and severe sepsis (9.1 +/- 18. 2 ng/ml and 145 +/- 70 mg/l) tall p = 0.005). CRP, but not PCT, levels were more elevated in severe sepsis than in SIPS (p < 0.0001). Higher PCT levels in the patients with four dysfunctional organs and higher PCT and CRP levels in nonsurvivors may only reflect the marked inflammatory response to septic shock. Conclusion: In this study, PCT and CPP had poor sensitivity and specificity for the diagnosis of infection. PCT did not clearly discriminate SIPS from sepsis or severe sepsis.