Aminopeptidase N (APN, CD13) is highly expressed on human monocytes. Activation of leucocyte subpopulations, such as T-cells, can induce CD13 expression. However, little is known about the physiological role of CD13 expression on human leucocytes. It was suggested that CD13, similar to other peptidases, could be involved in control of cell growth. The hypothesis that CD13 influences proliferation of monocytoid cells by retarding the velocity of the cell cycle was tested. It was shown that CD13 expression was modulated within the cell cycle. Cells entering the S-phase of cell cycle decreased their CD13 surface expression. Occupation of the active center of CD13 with artificial ligands such as monoclonal antibodies (mab) or the low molecular weight inhibitor actinonin induced a prolongation of cell cycle and decreased the rate of cell growth. Additionally, after ligation of CD13 by mab the complex of CD13 and monoclonal antibody was actively internalized into the cell. We suggest that CD13 could have important functions for the proliferation of human monocytoid cells. Here we show for the first time that occupation of the CD13 active center by antibodies or inhibitors influences the cell cycle and thereby diminishes cell growth rate. Occupation of the active center by antibodies or inhibitors might prevent cleavage or binding and internalization of still unknown natural substrate(s) and could evoke a deceleration of the cell cycle and reduced cell growth rate.