Chemotactic factors have been shown to induce aggregation and cellular swelling of rabbit polymorphonuclear neutrophils (PMN) obtained from the peritoneum. We examined the ability of the chemotactic fragment of C5 and the synthetic chemotactic tripeptide formyl-methionyl-leucyl-phenylalanine to induce these changes in various preparations of human leukocytes. We found that these factors did induce dextran-sedimented leukocytes and Ficoll-Hypaque-isolated PMN to aggregate and swell. Compared with rabbit peritoneal PMN, however, human PMN responded with more prominent swelling but with less prominent aggregation. Also unlike rabbit peritoneal PMN, human PMN adhered spontaneously to plastic surfaces; the chemotactic factors enhanced this adherence. Certain similarities between the responses of these two cell types were evident: in both rabbit peritoneal and isolated human peripheral PMN, the aggregates had a short life span in the fluid phase; in both, the number of aggregates formed was proportional to the log10 of the PMN concentration; and, in both, the chemotactic activity of the reagents paralleled their aggregating activity. In the system employed, lymphocytes were unresponsive to the chemotactic factors. Ficoll-Hypaque-isolated mononoclear cells (containing varying proportions of monocytes and lymphocytes) were responsive, indicating that human monocytes behave in a manner similar to the human PMN. The results suggest that chemotactic factors induce responsive cells to develop a hyperadherent cytoplasmic membrane. Aggregation and increased adhesiveness to plastic surfaces may reflect this induction.