The chemotactic activity of normal and diluted human serum and plasma for human monocytes and neutrophils was investigated. Undiluted, neither serum nor plasma attract monocytes, but this is attributable to an inhibitor masking chemotactic activity. When diluted 3- to 100-fold, appreciable activity for monocyte is detected. In contrast, chemotactic activity for neutrophils is already demonstrable in undiluted normal serum. Chemotactic activities are heat-labile, behave as pseudoglobulins, do not pass through a Diaflo PM 30 membrane and are not inactivated by treatment with di-isopropylfluorophosphate. They seem to be unrelated to the recognized components (or split products) of complement, kallikrein formation, clotting, fibrinolysis or isoantibody-blood cell-complement interaction. Upon complement activation of serum, neutrophil and monocyte chemotactic activities were generated which differed in several respects from the normal serum activities. The relative increase in activity upon activation of serum compared with normal serum was generally high for neutrophils but low for monocytes.