BACKGROUND: Procalcitonin (PCT) is a new marker of severe systemic bacterial infection. PCT consists of fragments katacalcin and calcitonin, which are precursors of calcitonin in thyroid. The source and role of PCT in pathogenesis of sepsis remains clarified. This study was focused on which subsets of peripheral blood mononuclear cells (PBMC) can induce PCT when they are stimulated with endotoxin or phorbol myristate acetate (PMA), and how the PCT production is controlled. MATERIALS AND METHODS: PBMC were isolated and incubated overnight in each media containing 1 ug/mL lipopolysaccharide (LPS), or 5 ng/mL PMA. Intracellular PCT was detected using fluorescein isothiocyanate (FITC) labeled anti-katacalcin antibody (Ab). Monocytes and lymphocytes were identified by phycoerythrin-conjugated CD14 Ab and CyChrome-conjugated CD3 Ab, respectively. Ten micrograms of soluble TNF receptor (sTNFR) were pretreated in PBMC 1 hr prior to adding the stimuli. Then, PBMC were analyzed using a flow cytometer. RESULTS: LPS increased intracellular PCT from 10.0 % to 27.2% in CD14-positive monocytes from healthy donors, but PMA induced more PCT production from 10.0% to 40.8%. (one representative, n=8). For CD3-p ositive lymphocytes, LPS did not stimulate PCT, but PMA increased PCT production by 2.35 fold (P<0.05, n=8). In the PBMC from the same donor, sTNFR highly decreased LPS-stimulated PCT (control 10.0%, LPS 27.2%, sTNFR 12.3%), but it did not significantly affect PMA-stimulated PCT. For sepsis patients, PMA stimulated more PCT than LPS did and PCT was more expressed compared with healthy donors. CONCLUSION: The PCT was produced in both monocytes and lymphocytes. PMA stimulated more PCT production than LPS did. The LPS-induced PCT production is partly mediated through TNF-alpha production.