A large number of clinical studies has described procalcitonin (ProCT) as a marker of bacterial infection and a good predictor of disease severity and antibiotherapy efficacy. Nevertheless, the mechanism of ProCT synthesis remains unclear. The aim of this study was to demonstrate potential ProCT production by peripheral blood mononuclear cells as is the case for cytokines involved in sepsis. In a whole blood model, LPS (10 micrograms/ml) stimulation on blood samples from healthy volunteers (n = 14) was tested. Early (TNF-alpha and IL1-beta) and late (IL-6 and IL-8) cytokines were produced in large amounts in contrast to the absence of ProCT. Additional experiments with nitric oxide or detection of intra-cellular ProCT (cell lysis, flow cytometry) had negative results. It was concluded that ProCT is not produced in this model. Data are still needed to investigate the cellular origin of ProCT in order to better define its clinical usefulness.