Objective: Raised plasma levels of procalcitonin (proCT) represent an early marker for septicaemia. They are related to disease severity and inversely to outcome and response to treatment. ProCT is presumably synthesised in tissues other than the thyroid C-cells which are the source of calcitonin (CT) in normal physiology. This study compares proCT and its cleavage products in the serum of patients with septicaemia with those in medullary thyroid carcinoma (MTC). Methods: Immunoreactive proCT and its cleavage products were extracted from the serum of patients with septicaemia or MTC using octadecylsilyl silica columns and characterised by reversed phase HPLC and Western blot analysis. ProCT, CT(1-32) and the flanking peptides PAS-57 and PDN-21 were recognised with antibodies specific for the individual peptides. Results: ProCT and a 10 kDa polypeptide were recognised with antibodies to PAS-57, CT(1-32) and PDN-21. An 8 kDa proCT fragment was detected with antibodies to CT and PDN-21. However, intact CT(1-32), PAS-57 and PDN-21, found in the serum of MTC patients, were undetectable. The results indicate partial cleavage of proCT in septicaemia different from that in MTC patients. Conclusions: ProCT and 10 and 8 kDa proCT fragments were recognised in the circulation of septic patients. They were different from the known proCT-processing products PAS-57, CT(1-32) and PDN-21 identified in the serum of normal subjects and of MTC patients. Distinct cleavage of proCT may contribute to the symptoms of septicaemia.