Procalcitonin (PCT), a precursor of calcitonin is a useful indicator of severe systemic infection and sepsis. For a better understanding of the pathophysiological background of PCT induction, a study was made of the intracellular expression of PCT in various human white blood cell populations-i.e. monocytes and polymorphonuclear granulocytes (PMNs)-and the role of TNF-alpha in the stimulation of their PCT production. The expression of PCT was investigated by flow cytometric analysis with intracellular staining with antibodies to the PCT components calcitonin (CT) and katacalcin (KC). Both human peripheral monocytes and granulocytes expressed PCT, and increased intracellular amounts of the PCT components were demonstrated after stimulation with Staphylococcus aureus as TNF-alpha inducer. The S. aureus induced stimulation of PCT production was inhibited by anti-TNF-alpha monoclonal antibodies. The monocytic cell line U937 expressed considerable intracellular PCT, but S. aureus failed to induce an increase in PCT expression. The determination of intracellular PCT by flow cytometry is a promising and a sensitive method for further investigation of the effects of various cytokines and cytokine-inducing agents in PCT synthesis of human monocytes and granulocytes.