Procalcitonin (PCT), the precursor of the hormone calcitonin, is a new parameter of inflammation. This acutephase hormokine seems to be more accurate for differentiating between bacterial infections and viral or non-infective causes of inflammation than other serological markers. PCT, which is induced in invasive bacterial infections, is routinely assayed in some intensive care, surgery, haematological units and emergency rooms to help determine the cause of a systemic inflammatory response syndrome (SIRS). Patients with systemic autoimmune diseases have a higher risk of developing severe systemic bacterial infections due to the disease itself and to the immunosuppressive therapy received. Distinguishing between infection and a disease flare is sometimes difficult. Strategies to reach a precise diagnosis are decisive to establish early, adequate patient management. Studies in febrile patients with systemic autoimmune diseases (systemic lupus erythematosus, antineutrophil cytoplasmic antibody-associated systemic vasculitis, and rheumatoid arthritis) suggest that elevated PCT concentrations offer good sensitivity and specificity for diagnosing systemic bacterial infection. Nevertheless, there is little published information on PCT levels in other autoimmune diseases and inflammatory processes. In this review we summarise the current evidence regarding the pathophysiological basis of systemic PCT production in sepsis and the results from current case series on the response of this peptide to infectious and non-infectious SIRS in systemic autoimmune diseases.