Only 20 to 40% of human blood monocytes were capable of responding to chemotaxins in vitro. This limit is not due to restrictions of the in vitro system, but is due to the existence of a migrating subpopulation. Over a wide range, the number of cells migrating toward a given concentration of chemotaxin was directly proportional to the number added to the chemotaxis chamber. These monocytes responded to all of the three stimuli used: human serum-derived C5a, human lymphocyte-derived chemotactic factor, and a synthetic peptide. It was possible to deactivate cells to one attractant, leaving the response to other attractants intact. This suggested that these attractants were recognized by different receptors. Several lines of evidence showed that most migrating cells had receptors for all three chemotaxins tested. Thus, if cells were assayed for migration to one attractant, no additional migration occurred when the remaining cells were assayed for migration to a different attractant. Furthermore, the same cells that had migrated toward one attractant were able to respond to other chemotaxins. We also found that a single attractant attracted as many cells as a combination of two or three attractants. Calculations from these data showed that at least 75% of the migrating monocytes have different receptors for all three attractants.